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The definition of “hospitalist,” according to the SHM website, is a clinician “dedicated to delivering comprehensive medical care to hospitalized patients.” For years, the hospital setting was the specialties’ identifier. But as hospitalists’ scope has expanded, and post-acute care (PAC) in the United States has grown, more hospitalists are extending their roles into this space.
PAC today is more than the traditional nursing home, according to Manoj K. Mathew, MD, SFHM, national medical director of Agilon Health in Los Angeles.
Many of those expanded settings Dr. Mathew describes emerged as a result of the Affordable Care Act. Since its enactment in 2010, the ACA has heightened providers’ focus on the “Triple Aim” of improving the patient experience (including quality and satisfaction), improving the health of populations, and reducing the per capita cost of healthcare.1 Vishal Kuchaculla, MD, New England regional post-acute medical director of Knoxville,Tenn.-based TeamHealth, says new service lines also developed as Medicare clamped down on long-term inpatient hospital stays by giving financial impetus to discharge patients as soon as possible.
“Over the last few years, there’s been a major shift from fee-for-service to risk-based payment models,” Dr. Kuchaculla says. “The government’s financial incentives are driving outcomes to improve performance initiatives.”
“Today, LTACHs can be used as substitutes for short-term acute care,” says Sean R. Muldoon, MD, MPH, FCCP, chief medical officer of Kindred Healthcare in Louisville, Ky., and former chair of SHM’s Post-Acute Care Committee. “This means that a patient can be directly admitted from their home to an LTACH. In fact, many hospice and home-care patients are referred from physicians’ offices without a preceding hospitalization.”
122259_Medicare_claims web.PNG
Hospitalists can fill a need
More hospitalists are working in PACs for a number of reasons. Dr. Mathew says PAC facilities and services have “typically lacked the clinical structure and processes to obtain the results that patients and payors expect.
“These deficits needed to be quickly remedied as patients discharged from hospitals have increased acuity and higher disease burdens,” he adds. “Hospitalists were the natural choice to fill roles requiring their expertise and experience.”
Dr. Muldoon considers the expanded scope of practice into PACs an additional layer to hospital medicine’s value proposition to the healthcare system.
“As experts in the management of inpatient populations, it’s natural for hospitalists to expand to other facilities with inpatient-like populations,” he says, noting SNFs are the most popular choice, with IRFs and LTACHs also being common places to work. Few hospitalists work in home care or hospice.
PAC settings are designed to help patients who are transitioning from an inpatient setting back to their home or other setting.
“Many patients go home after a SNF stay, while others will move to a nursing home or other longer-term care setting for the first time,” says Tiffany Radcliff, PhD, a health economist in the department of health policy and management at Texas A&M University School of Public Health in College Station. “With this in mind, hospitalists working in PAC have the opportunity to address each patient’s ongoing care needs and prepare them for their next setting. Hospitalists can manage medication or other care regimen changes that resulted from an inpatient stay, reinforce discharge instructions to the patient and their caregivers, and identify any other issues with continuing care that need to be addressed before discharge to the next care setting.”
Transitioning Care
Even if a hospitalist is not employed at a PAC, it’s important that they know something about them.
“As patients are moved downstream earlier, hospitalists are being asked to help make a judgment regarding when and where an inpatient is transitioned,” Dr. Muldoon says. As organizations move toward becoming fully risk capable, it is necessary to develop referral networks of high-quality PAC providers to achieve the best clinical outcomes, reduce readmissions, and lower costs.2“Therefore, hospitalists should have a working knowledge of the different sites of service as well as some opinion on the suitability of available options in their community,” Dr. Muldoon says. “The hospitalist can also help to educate the hospitalized patient on what to expect at a PAC.”
If a patient is inappropriately prepared for the PAC setting, it could lead to incomplete management of their condition, which ultimately could lead to readmission.
“When hospitalists know how care is provided in a PAC setting, they are better able to ensure a smoother transition of care between settings,” says Tochi Iroku-Malize, MD, MPH, MBA, FAAFP, SFHM, chair of family medicine at Northwell Health in Long Island, N.Y. “This will ultimately prevent unnecessary readmissions.”
Further, the quality metrics that hospitals and thereby hospitalists are judged by no longer end at the hospital’s exit.
“The ownership of acute-care outcomes requires extending the accountability to outside of the institution’s four walls,” Dr. Mathew says. “The inpatient team needs to place great importance on the transition of care and the subsequent quality of that care when the patient is discharged.”
Robert W. Harrington Jr., MD, SFHM, chief medical officer of Plano, Texas–based Reliant Post-Acute Care Solutions and former SHM president, says the health system landscapes are pushing HM beyond the hospitals’ walls.
How PAC settings differ from hospitals
Practicing in PAC has some important nuances that hospitalists from short-term acute care need to get accustomed to, Dr. Muldoon says. Primarily, the diagnostic capabilities are much more limited, as is the presence of high-level staffing. Further, patients are less resilient to medication changes and interventions, so changes need to be done gradually.
“Hospitalists who try to practice acute-care medicine in a PAC setting may become frustrated by the length of time it takes to do a work-up, get a consultation, and respond to a patient’s change of condition,” Dr. Muldoon says. “Nonetheless, hospitalists can overcome this once recognizing this mind shift.”
According to Dr. Harrington, another challenge hospitalists may face is the inability of the hospital’s and PAC facility’s IT platforms to exchange electronic information.
“The major vendors on both sides need to figure out an interoperability strategy,” he says. “Currently, it often takes 1-3 days to receive a new patient’s discharge summary. The summary may consist of a stack of paper that takes significant time to sort through and requires the PAC facility to perform duplicate data entry. It’s a very highly inefficient process that opens up the doors to mistakes and errors of omission and commission that can result in bad patient outcomes.”
Arif Nazir, MD, CMD, FACP, AGSF, chief medical officer of Signature HealthCARE and president of SHC Medical Partners, both in Louisville, Ky., cites additional reasons the lack of seamless communication between a hospital and PAC facility is problematic. “I see physicians order laboratory tests and investigations that were already done in the hospital because they didn’t know they were already performed or never received the results,” he says. “Similarly, I see patients continue to take medications prescribed in the hospital long term even though they were only supposed to take them short term. I’ve also seen patients come to a PAC setting from a hospital without any formal understanding of their rehabilitative period and expectations for recovery.”
What’s ahead?
Looking to the future, Surafel Tsega, MD, clinical instructor at Mount Sinai Hospital in New York, says he thinks there will be a move toward greater collaboration among inpatient and PAC facilities, particularly in the discharge process, given that hospitals have an added incentive to ensure safe transitions because reimbursement from the Centers for Medicare & Medicaid Services is tied to readmissions and there are penalties for readmission. This involves more comprehensive planning regarding “warm handoffs” (e.g., real-time discussions with PAC providers about a patient’s hospital course and plan of care upon discharge), transferring of information, and so forth.
And while it can still be challenging to identify high-risk patients or determine the intensity and duration of their care, Dr. Mathew says risk-stratification tools and care pathways are continually being refined to maximize value with the limited resources available. In addition, with an increased emphasis on employing a team approach to care, there will be better integration of non-medical services to address the social determinants of health, which play significant roles in overall health and healing.
“Working with community-based organizations for this purpose will be a valuable tool for any of the population health–based initiatives,” he says.
Dr. Muldoon says he believes healthcare reform will increasingly view an inpatient admission as something to be avoided.
“If hospitalization can’t be avoided, then it should be shortened as much as possible,” he says. “This will shift inpatient care into LTACHs, SNFs, and IRFs. Hospitalists would be wise to follow patients into those settings as traditional inpatient census is reduced. This will take a few years, so hospitalists should start now in preparing for that downstream transition of individuals who were previously inpatients.”
The cost of care, and other PAC facts and figures
The amount of money that Medicare spends on post-acute care (PAC) has been increasing. In 2012, 12.6% of Medicare beneficiaries used some form of PAC, costing $62 billion.2 That amounts to the Centers for Medicare & Medicaid Services spending close to 25% of Medicare beneficiary expenses on PAC, a 133% increase from 2001 to 2012. Among the different types, $30.4 billion was spent on skilled nursing facilities (SNFs), $18.6 billion on home health, and $13.1 billion on long-term acute care (LTAC) and acute-care rehabilitation.2
It’s also been reported that after short-term acute-care hospitalization, about one in five Medicare beneficiaries requires continued specialized treatment in one of the three typical Medicare PAC settings: inpatient rehabilitation facilities (IRFs), LTAC hospitals, and SNFs.3
What’s more, hospital readmission nearly doubles the cost of an episode, so the financial implications for organizations operating in risk-bearing arrangements are significant. In 2013, 2,213 hospitals were charged $280 million in readmission penalties.2
References
1. The role of post-acute care in new care delivery models. American Hospital Association website. Available at: http://www.aha.org/research/reports/tw/15dec-tw-postacute.pdf. Accessed Nov. 7, 2016.
2. Post-acute care integration: Today and in the future. DHG Healthcare website. Available at: http://www2.dhgllp.com/res_pubs/HCG-Post-Acute-Care-Integration.pdf. Accessed Nov. 7, 2016.
3. Overview: Post-acute care transitions toolkit. Society for Hospital Medicine website. Available at: http://www.hospitalmedicine.org/Web/Quality___Innovation/Implementation_Toolkit/pact/Overview_PACT.aspx?hkey=dea3da3c-8620-46db-a00f-89f07f021958. Accessed Nov. 10, 2016.
The definition of “hospitalist,” according to the SHM website, is a clinician “dedicated to delivering comprehensive medical care to hospitalized patients.” For years, the hospital setting was the specialties’ identifier. But as hospitalists’ scope has expanded, and post-acute care (PAC) in the United States has grown, more hospitalists are extending their roles into this space.
PAC today is more than the traditional nursing home, according to Manoj K. Mathew, MD, SFHM, national medical director of Agilon Health in Los Angeles.
Many of those expanded settings Dr. Mathew describes emerged as a result of the Affordable Care Act. Since its enactment in 2010, the ACA has heightened providers’ focus on the “Triple Aim” of improving the patient experience (including quality and satisfaction), improving the health of populations, and reducing the per capita cost of healthcare.1 Vishal Kuchaculla, MD, New England regional post-acute medical director of Knoxville,Tenn.-based TeamHealth, says new service lines also developed as Medicare clamped down on long-term inpatient hospital stays by giving financial impetus to discharge patients as soon as possible.
“Over the last few years, there’s been a major shift from fee-for-service to risk-based payment models,” Dr. Kuchaculla says. “The government’s financial incentives are driving outcomes to improve performance initiatives.”
“Today, LTACHs can be used as substitutes for short-term acute care,” says Sean R. Muldoon, MD, MPH, FCCP, chief medical officer of Kindred Healthcare in Louisville, Ky., and former chair of SHM’s Post-Acute Care Committee. “This means that a patient can be directly admitted from their home to an LTACH. In fact, many hospice and home-care patients are referred from physicians’ offices without a preceding hospitalization.”
122259_Medicare_claims web.PNG
Hospitalists can fill a need
More hospitalists are working in PACs for a number of reasons. Dr. Mathew says PAC facilities and services have “typically lacked the clinical structure and processes to obtain the results that patients and payors expect.
“These deficits needed to be quickly remedied as patients discharged from hospitals have increased acuity and higher disease burdens,” he adds. “Hospitalists were the natural choice to fill roles requiring their expertise and experience.”
Dr. Muldoon considers the expanded scope of practice into PACs an additional layer to hospital medicine’s value proposition to the healthcare system.
“As experts in the management of inpatient populations, it’s natural for hospitalists to expand to other facilities with inpatient-like populations,” he says, noting SNFs are the most popular choice, with IRFs and LTACHs also being common places to work. Few hospitalists work in home care or hospice.
PAC settings are designed to help patients who are transitioning from an inpatient setting back to their home or other setting.
“Many patients go home after a SNF stay, while others will move to a nursing home or other longer-term care setting for the first time,” says Tiffany Radcliff, PhD, a health economist in the department of health policy and management at Texas A&M University School of Public Health in College Station. “With this in mind, hospitalists working in PAC have the opportunity to address each patient’s ongoing care needs and prepare them for their next setting. Hospitalists can manage medication or other care regimen changes that resulted from an inpatient stay, reinforce discharge instructions to the patient and their caregivers, and identify any other issues with continuing care that need to be addressed before discharge to the next care setting.”
Transitioning Care
Even if a hospitalist is not employed at a PAC, it’s important that they know something about them.
“As patients are moved downstream earlier, hospitalists are being asked to help make a judgment regarding when and where an inpatient is transitioned,” Dr. Muldoon says. As organizations move toward becoming fully risk capable, it is necessary to develop referral networks of high-quality PAC providers to achieve the best clinical outcomes, reduce readmissions, and lower costs.2“Therefore, hospitalists should have a working knowledge of the different sites of service as well as some opinion on the suitability of available options in their community,” Dr. Muldoon says. “The hospitalist can also help to educate the hospitalized patient on what to expect at a PAC.”
If a patient is inappropriately prepared for the PAC setting, it could lead to incomplete management of their condition, which ultimately could lead to readmission.
“When hospitalists know how care is provided in a PAC setting, they are better able to ensure a smoother transition of care between settings,” says Tochi Iroku-Malize, MD, MPH, MBA, FAAFP, SFHM, chair of family medicine at Northwell Health in Long Island, N.Y. “This will ultimately prevent unnecessary readmissions.”
Further, the quality metrics that hospitals and thereby hospitalists are judged by no longer end at the hospital’s exit.
“The ownership of acute-care outcomes requires extending the accountability to outside of the institution’s four walls,” Dr. Mathew says. “The inpatient team needs to place great importance on the transition of care and the subsequent quality of that care when the patient is discharged.”
Robert W. Harrington Jr., MD, SFHM, chief medical officer of Plano, Texas–based Reliant Post-Acute Care Solutions and former SHM president, says the health system landscapes are pushing HM beyond the hospitals’ walls.
How PAC settings differ from hospitals
Practicing in PAC has some important nuances that hospitalists from short-term acute care need to get accustomed to, Dr. Muldoon says. Primarily, the diagnostic capabilities are much more limited, as is the presence of high-level staffing. Further, patients are less resilient to medication changes and interventions, so changes need to be done gradually.
“Hospitalists who try to practice acute-care medicine in a PAC setting may become frustrated by the length of time it takes to do a work-up, get a consultation, and respond to a patient’s change of condition,” Dr. Muldoon says. “Nonetheless, hospitalists can overcome this once recognizing this mind shift.”
According to Dr. Harrington, another challenge hospitalists may face is the inability of the hospital’s and PAC facility’s IT platforms to exchange electronic information.
“The major vendors on both sides need to figure out an interoperability strategy,” he says. “Currently, it often takes 1-3 days to receive a new patient’s discharge summary. The summary may consist of a stack of paper that takes significant time to sort through and requires the PAC facility to perform duplicate data entry. It’s a very highly inefficient process that opens up the doors to mistakes and errors of omission and commission that can result in bad patient outcomes.”
Arif Nazir, MD, CMD, FACP, AGSF, chief medical officer of Signature HealthCARE and president of SHC Medical Partners, both in Louisville, Ky., cites additional reasons the lack of seamless communication between a hospital and PAC facility is problematic. “I see physicians order laboratory tests and investigations that were already done in the hospital because they didn’t know they were already performed or never received the results,” he says. “Similarly, I see patients continue to take medications prescribed in the hospital long term even though they were only supposed to take them short term. I’ve also seen patients come to a PAC setting from a hospital without any formal understanding of their rehabilitative period and expectations for recovery.”
What’s ahead?
Looking to the future, Surafel Tsega, MD, clinical instructor at Mount Sinai Hospital in New York, says he thinks there will be a move toward greater collaboration among inpatient and PAC facilities, particularly in the discharge process, given that hospitals have an added incentive to ensure safe transitions because reimbursement from the Centers for Medicare & Medicaid Services is tied to readmissions and there are penalties for readmission. This involves more comprehensive planning regarding “warm handoffs” (e.g., real-time discussions with PAC providers about a patient’s hospital course and plan of care upon discharge), transferring of information, and so forth.
And while it can still be challenging to identify high-risk patients or determine the intensity and duration of their care, Dr. Mathew says risk-stratification tools and care pathways are continually being refined to maximize value with the limited resources available. In addition, with an increased emphasis on employing a team approach to care, there will be better integration of non-medical services to address the social determinants of health, which play significant roles in overall health and healing.
“Working with community-based organizations for this purpose will be a valuable tool for any of the population health–based initiatives,” he says.
Dr. Muldoon says he believes healthcare reform will increasingly view an inpatient admission as something to be avoided.
“If hospitalization can’t be avoided, then it should be shortened as much as possible,” he says. “This will shift inpatient care into LTACHs, SNFs, and IRFs. Hospitalists would be wise to follow patients into those settings as traditional inpatient census is reduced. This will take a few years, so hospitalists should start now in preparing for that downstream transition of individuals who were previously inpatients.”
The cost of care, and other PAC facts and figures
The amount of money that Medicare spends on post-acute care (PAC) has been increasing. In 2012, 12.6% of Medicare beneficiaries used some form of PAC, costing $62 billion.2 That amounts to the Centers for Medicare & Medicaid Services spending close to 25% of Medicare beneficiary expenses on PAC, a 133% increase from 2001 to 2012. Among the different types, $30.4 billion was spent on skilled nursing facilities (SNFs), $18.6 billion on home health, and $13.1 billion on long-term acute care (LTAC) and acute-care rehabilitation.2
It’s also been reported that after short-term acute-care hospitalization, about one in five Medicare beneficiaries requires continued specialized treatment in one of the three typical Medicare PAC settings: inpatient rehabilitation facilities (IRFs), LTAC hospitals, and SNFs.3
What’s more, hospital readmission nearly doubles the cost of an episode, so the financial implications for organizations operating in risk-bearing arrangements are significant. In 2013, 2,213 hospitals were charged $280 million in readmission penalties.2
References
1. The role of post-acute care in new care delivery models. American Hospital Association website. Available at: http://www.aha.org/research/reports/tw/15dec-tw-postacute.pdf. Accessed Nov. 7, 2016.
2. Post-acute care integration: Today and in the future. DHG Healthcare website. Available at: http://www2.dhgllp.com/res_pubs/HCG-Post-Acute-Care-Integration.pdf. Accessed Nov. 7, 2016.
3. Overview: Post-acute care transitions toolkit. Society for Hospital Medicine website. Available at: http://www.hospitalmedicine.org/Web/Quality___Innovation/Implementation_Toolkit/pact/Overview_PACT.aspx?hkey=dea3da3c-8620-46db-a00f-89f07f021958. Accessed Nov. 10, 2016.
The definition of “hospitalist,” according to the SHM website, is a clinician “dedicated to delivering comprehensive medical care to hospitalized patients.” For years, the hospital setting was the specialties’ identifier. But as hospitalists’ scope has expanded, and post-acute care (PAC) in the United States has grown, more hospitalists are extending their roles into this space.
PAC today is more than the traditional nursing home, according to Manoj K. Mathew, MD, SFHM, national medical director of Agilon Health in Los Angeles.
Many of those expanded settings Dr. Mathew describes emerged as a result of the Affordable Care Act. Since its enactment in 2010, the ACA has heightened providers’ focus on the “Triple Aim” of improving the patient experience (including quality and satisfaction), improving the health of populations, and reducing the per capita cost of healthcare.1 Vishal Kuchaculla, MD, New England regional post-acute medical director of Knoxville,Tenn.-based TeamHealth, says new service lines also developed as Medicare clamped down on long-term inpatient hospital stays by giving financial impetus to discharge patients as soon as possible.
“Over the last few years, there’s been a major shift from fee-for-service to risk-based payment models,” Dr. Kuchaculla says. “The government’s financial incentives are driving outcomes to improve performance initiatives.”
“Today, LTACHs can be used as substitutes for short-term acute care,” says Sean R. Muldoon, MD, MPH, FCCP, chief medical officer of Kindred Healthcare in Louisville, Ky., and former chair of SHM’s Post-Acute Care Committee. “This means that a patient can be directly admitted from their home to an LTACH. In fact, many hospice and home-care patients are referred from physicians’ offices without a preceding hospitalization.”
122259_Medicare_claims web.PNG
Hospitalists can fill a need
More hospitalists are working in PACs for a number of reasons. Dr. Mathew says PAC facilities and services have “typically lacked the clinical structure and processes to obtain the results that patients and payors expect.
“These deficits needed to be quickly remedied as patients discharged from hospitals have increased acuity and higher disease burdens,” he adds. “Hospitalists were the natural choice to fill roles requiring their expertise and experience.”
Dr. Muldoon considers the expanded scope of practice into PACs an additional layer to hospital medicine’s value proposition to the healthcare system.
“As experts in the management of inpatient populations, it’s natural for hospitalists to expand to other facilities with inpatient-like populations,” he says, noting SNFs are the most popular choice, with IRFs and LTACHs also being common places to work. Few hospitalists work in home care or hospice.
PAC settings are designed to help patients who are transitioning from an inpatient setting back to their home or other setting.
“Many patients go home after a SNF stay, while others will move to a nursing home or other longer-term care setting for the first time,” says Tiffany Radcliff, PhD, a health economist in the department of health policy and management at Texas A&M University School of Public Health in College Station. “With this in mind, hospitalists working in PAC have the opportunity to address each patient’s ongoing care needs and prepare them for their next setting. Hospitalists can manage medication or other care regimen changes that resulted from an inpatient stay, reinforce discharge instructions to the patient and their caregivers, and identify any other issues with continuing care that need to be addressed before discharge to the next care setting.”
Transitioning Care
Even if a hospitalist is not employed at a PAC, it’s important that they know something about them.
“As patients are moved downstream earlier, hospitalists are being asked to help make a judgment regarding when and where an inpatient is transitioned,” Dr. Muldoon says. As organizations move toward becoming fully risk capable, it is necessary to develop referral networks of high-quality PAC providers to achieve the best clinical outcomes, reduce readmissions, and lower costs.2“Therefore, hospitalists should have a working knowledge of the different sites of service as well as some opinion on the suitability of available options in their community,” Dr. Muldoon says. “The hospitalist can also help to educate the hospitalized patient on what to expect at a PAC.”
If a patient is inappropriately prepared for the PAC setting, it could lead to incomplete management of their condition, which ultimately could lead to readmission.
“When hospitalists know how care is provided in a PAC setting, they are better able to ensure a smoother transition of care between settings,” says Tochi Iroku-Malize, MD, MPH, MBA, FAAFP, SFHM, chair of family medicine at Northwell Health in Long Island, N.Y. “This will ultimately prevent unnecessary readmissions.”
Further, the quality metrics that hospitals and thereby hospitalists are judged by no longer end at the hospital’s exit.
“The ownership of acute-care outcomes requires extending the accountability to outside of the institution’s four walls,” Dr. Mathew says. “The inpatient team needs to place great importance on the transition of care and the subsequent quality of that care when the patient is discharged.”
Robert W. Harrington Jr., MD, SFHM, chief medical officer of Plano, Texas–based Reliant Post-Acute Care Solutions and former SHM president, says the health system landscapes are pushing HM beyond the hospitals’ walls.
How PAC settings differ from hospitals
Practicing in PAC has some important nuances that hospitalists from short-term acute care need to get accustomed to, Dr. Muldoon says. Primarily, the diagnostic capabilities are much more limited, as is the presence of high-level staffing. Further, patients are less resilient to medication changes and interventions, so changes need to be done gradually.
“Hospitalists who try to practice acute-care medicine in a PAC setting may become frustrated by the length of time it takes to do a work-up, get a consultation, and respond to a patient’s change of condition,” Dr. Muldoon says. “Nonetheless, hospitalists can overcome this once recognizing this mind shift.”
According to Dr. Harrington, another challenge hospitalists may face is the inability of the hospital’s and PAC facility’s IT platforms to exchange electronic information.
“The major vendors on both sides need to figure out an interoperability strategy,” he says. “Currently, it often takes 1-3 days to receive a new patient’s discharge summary. The summary may consist of a stack of paper that takes significant time to sort through and requires the PAC facility to perform duplicate data entry. It’s a very highly inefficient process that opens up the doors to mistakes and errors of omission and commission that can result in bad patient outcomes.”
Arif Nazir, MD, CMD, FACP, AGSF, chief medical officer of Signature HealthCARE and president of SHC Medical Partners, both in Louisville, Ky., cites additional reasons the lack of seamless communication between a hospital and PAC facility is problematic. “I see physicians order laboratory tests and investigations that were already done in the hospital because they didn’t know they were already performed or never received the results,” he says. “Similarly, I see patients continue to take medications prescribed in the hospital long term even though they were only supposed to take them short term. I’ve also seen patients come to a PAC setting from a hospital without any formal understanding of their rehabilitative period and expectations for recovery.”
What’s ahead?
Looking to the future, Surafel Tsega, MD, clinical instructor at Mount Sinai Hospital in New York, says he thinks there will be a move toward greater collaboration among inpatient and PAC facilities, particularly in the discharge process, given that hospitals have an added incentive to ensure safe transitions because reimbursement from the Centers for Medicare & Medicaid Services is tied to readmissions and there are penalties for readmission. This involves more comprehensive planning regarding “warm handoffs” (e.g., real-time discussions with PAC providers about a patient’s hospital course and plan of care upon discharge), transferring of information, and so forth.
And while it can still be challenging to identify high-risk patients or determine the intensity and duration of their care, Dr. Mathew says risk-stratification tools and care pathways are continually being refined to maximize value with the limited resources available. In addition, with an increased emphasis on employing a team approach to care, there will be better integration of non-medical services to address the social determinants of health, which play significant roles in overall health and healing.
“Working with community-based organizations for this purpose will be a valuable tool for any of the population health–based initiatives,” he says.
Dr. Muldoon says he believes healthcare reform will increasingly view an inpatient admission as something to be avoided.
“If hospitalization can’t be avoided, then it should be shortened as much as possible,” he says. “This will shift inpatient care into LTACHs, SNFs, and IRFs. Hospitalists would be wise to follow patients into those settings as traditional inpatient census is reduced. This will take a few years, so hospitalists should start now in preparing for that downstream transition of individuals who were previously inpatients.”
The cost of care, and other PAC facts and figures
The amount of money that Medicare spends on post-acute care (PAC) has been increasing. In 2012, 12.6% of Medicare beneficiaries used some form of PAC, costing $62 billion.2 That amounts to the Centers for Medicare & Medicaid Services spending close to 25% of Medicare beneficiary expenses on PAC, a 133% increase from 2001 to 2012. Among the different types, $30.4 billion was spent on skilled nursing facilities (SNFs), $18.6 billion on home health, and $13.1 billion on long-term acute care (LTAC) and acute-care rehabilitation.2
It’s also been reported that after short-term acute-care hospitalization, about one in five Medicare beneficiaries requires continued specialized treatment in one of the three typical Medicare PAC settings: inpatient rehabilitation facilities (IRFs), LTAC hospitals, and SNFs.3
What’s more, hospital readmission nearly doubles the cost of an episode, so the financial implications for organizations operating in risk-bearing arrangements are significant. In 2013, 2,213 hospitals were charged $280 million in readmission penalties.2
References
1. The role of post-acute care in new care delivery models. American Hospital Association website. Available at: http://www.aha.org/research/reports/tw/15dec-tw-postacute.pdf. Accessed Nov. 7, 2016.
2. Post-acute care integration: Today and in the future. DHG Healthcare website. Available at: http://www2.dhgllp.com/res_pubs/HCG-Post-Acute-Care-Integration.pdf. Accessed Nov. 7, 2016.
3. Overview: Post-acute care transitions toolkit. Society for Hospital Medicine website. Available at: http://www.hospitalmedicine.org/Web/Quality___Innovation/Implementation_Toolkit/pact/Overview_PACT.aspx?hkey=dea3da3c-8620-46db-a00f-89f07f021958. Accessed Nov. 10, 2016.
Transplantation palliative care: The time is ripe
Over 10 years ago, a challenge was made in a surgical publication for increased collaboration between the fields of transplantation and palliative care.1
Since that time not much progress has been made bringing these fields together in a consistent way that would mutually benefit patients and the specialties. However, other progress has been made, particularly in the field of palliative care, which could brighten the prospects and broaden the opportunities to accomplish collaboration between palliative care and transplantation.
Growth of palliative services
During the past decade there has been a robust proliferation of hospital-based palliative care programs in the United States. In all, 67% of U.S. hospitals with 50 or more beds report palliative care teams, up from 63% in 2011 and 53% in 2008.
Only a decade ago, critical care and palliative care were generally considered mutually exclusive. Evidence is trickling in to suggest that this is no longer the case. Although palliative care was not an integral part of critical care at that time, patients, families, and even practitioners began to demand these services. Cook and Rocker have eloquently advocated the rightful place of palliative care in the ICU.2
Studies in recent years have shown that the integration of palliative care into critical care decreases in length of ICU and hospital stay, decreases costs, enhances patient/family satisfaction, and promotes a more rapid consensus about goals of care, without increasing mortality. The ICU experience to date could be considered a reassuring precedent for transplantation palliative care.
Integration of palliative care with transplantation
Early palliative care intervention has been shown to improve symptom burden and depression scores in end-stage liver disease patients awaiting transplant. In addition, early palliative care consultation in conjunction with cancer treatment has been associated with increased survival in non–small-cell lung cancer patients. It has been demonstrated that early integration of palliative care in the surgical ICU alongside disease-directed curative care can be accomplished without change in mortality, while improving end-of-life practice in liver transplant patients.3
What palliative care can do for transplant patients
What does palliative care mean for the person (and family) awaiting transplantation? For the cirrhotic patient with cachexia, ascites, and encephalopathy, it means access to the services of a team trained in the management of these symptoms. Palliative care teams can also provide psychosocial and spiritual support for patients and families who are intimidated by the complex navigation of the health care system and the existential threat that end-stage organ failure presents to them. Skilled palliative care and services can be the difference between failing and extended life with a higher quality of life for these very sick patients
Resuscitation of a patient, whether through restoration of organ function or interdicting the progression of disease, begins with resuscitation of hope. Nothing achieves this more quickly than amelioration of burdensome symptoms for the patient and family.
The barriers for transplant surgeons and teams referring and incorporating palliative care services in their practices are multiple and profound. The unique dilemma facing the transplant team is to balance the treatment of the failing organ, the treatment of the patient (and family and friends), and the best use of the graft, a precious gift of society.
Palliative surgery has been defined as any invasive procedure in which the main intention is to mitigate physical symptoms in patients with noncurable disease without causing premature death. The very success of transplantation over the past 3 decades has obscured our memory of transplantation as a type of palliative surgery. It is a well-known axiom of reconstructive surgery that the reconstructed site should be compared to what was there, not to “normal.” Even in the current era of improved immunosuppression and posttransplant support services, one could hardly describe even a successful transplant patient’s experience as “normal.” These patients’ lives may be extended and/or enhanced but they need palliative care before, during, and after transplantation. The growing availability of trained palliative care clinicians and teams, the increased familiarity of palliative and end-of-life care to surgical residents and fellows, and quality metrics measuring palliative care outcomes will provide reassurance and guidance to address reservations about the convergence of the two seemingly opposite realities.
A modest proposal
We propose that palliative care be presented to the entire spectrum of transplantation care: on the ward, in the ICU, and after transplantation. More specific “triggers” for palliative care for referral of transplant patients should be identified. Wentlandt et al.4 have described a promising model for an ambulatory clinic, which provides early, integrated palliative care to patients awaiting and receiving organ transplantation. In addition, we propose an application for grant funding for a conference and eventual formation of a work group of transplant surgeons and team members, palliative care clinicians, and patient/families who have experienced one of the aspects of the transplant spectrum. We await the subspecialty certification in hospice and palliative medicine of a transplant surgeon. Outside of transplantation, every other surgical specialty in the United States has diplomates certified in hospice and palliative medicine. We await the benefits that will accrue from research about the merging of these fields.
1. Molmenti EP, Dunn GP: Transplantation and palliative care: The convergence of two seemingly opposite realities. Surg Clin North Am. 2005;85:373-82.
2. Cook D, Rocker G. Dying with dignity in the intensive care unit. N Engl J Med. 2014;370:2506-14.
3. Lamba S, Murphy P, McVicker S, Smith JH, and Mosenthal AC. Changing end-of-life care practice for liver transplant patients: structured palliative care intervention in the surgical intensive care unit. J Pain Symptom Manage. 2012; 44(4):508-19.
4. Wentlandt, K., Dall’Osto, A., Freeman, N., Le, L. W., Kaya, E., Ross, H., Singer, L. G., Abbey, S., Clarke, H. and Zimmermann, C. (2016), The Transplant Palliative Care Clinic: An early palliative care model for patients in a transplant program. Clin Transplant. 2016 Nov 4; doi: 10.1111/ctr.12838.
Dr. Azoulay is a transplantation specialist of Assistance Publique – Hôpitaux de Paris, and the University of Paris. Dr. Dunn is medical director of the Palliative Care Consultation Service at the University of Pittsburgh Medical Center Hamot, and vice-chair of the ACS Committee on Surgical Palliative Care.
Over 10 years ago, a challenge was made in a surgical publication for increased collaboration between the fields of transplantation and palliative care.1
Since that time not much progress has been made bringing these fields together in a consistent way that would mutually benefit patients and the specialties. However, other progress has been made, particularly in the field of palliative care, which could brighten the prospects and broaden the opportunities to accomplish collaboration between palliative care and transplantation.
Growth of palliative services
During the past decade there has been a robust proliferation of hospital-based palliative care programs in the United States. In all, 67% of U.S. hospitals with 50 or more beds report palliative care teams, up from 63% in 2011 and 53% in 2008.
Only a decade ago, critical care and palliative care were generally considered mutually exclusive. Evidence is trickling in to suggest that this is no longer the case. Although palliative care was not an integral part of critical care at that time, patients, families, and even practitioners began to demand these services. Cook and Rocker have eloquently advocated the rightful place of palliative care in the ICU.2
Studies in recent years have shown that the integration of palliative care into critical care decreases in length of ICU and hospital stay, decreases costs, enhances patient/family satisfaction, and promotes a more rapid consensus about goals of care, without increasing mortality. The ICU experience to date could be considered a reassuring precedent for transplantation palliative care.
Integration of palliative care with transplantation
Early palliative care intervention has been shown to improve symptom burden and depression scores in end-stage liver disease patients awaiting transplant. In addition, early palliative care consultation in conjunction with cancer treatment has been associated with increased survival in non–small-cell lung cancer patients. It has been demonstrated that early integration of palliative care in the surgical ICU alongside disease-directed curative care can be accomplished without change in mortality, while improving end-of-life practice in liver transplant patients.3
What palliative care can do for transplant patients
What does palliative care mean for the person (and family) awaiting transplantation? For the cirrhotic patient with cachexia, ascites, and encephalopathy, it means access to the services of a team trained in the management of these symptoms. Palliative care teams can also provide psychosocial and spiritual support for patients and families who are intimidated by the complex navigation of the health care system and the existential threat that end-stage organ failure presents to them. Skilled palliative care and services can be the difference between failing and extended life with a higher quality of life for these very sick patients
Resuscitation of a patient, whether through restoration of organ function or interdicting the progression of disease, begins with resuscitation of hope. Nothing achieves this more quickly than amelioration of burdensome symptoms for the patient and family.
The barriers for transplant surgeons and teams referring and incorporating palliative care services in their practices are multiple and profound. The unique dilemma facing the transplant team is to balance the treatment of the failing organ, the treatment of the patient (and family and friends), and the best use of the graft, a precious gift of society.
Palliative surgery has been defined as any invasive procedure in which the main intention is to mitigate physical symptoms in patients with noncurable disease without causing premature death. The very success of transplantation over the past 3 decades has obscured our memory of transplantation as a type of palliative surgery. It is a well-known axiom of reconstructive surgery that the reconstructed site should be compared to what was there, not to “normal.” Even in the current era of improved immunosuppression and posttransplant support services, one could hardly describe even a successful transplant patient’s experience as “normal.” These patients’ lives may be extended and/or enhanced but they need palliative care before, during, and after transplantation. The growing availability of trained palliative care clinicians and teams, the increased familiarity of palliative and end-of-life care to surgical residents and fellows, and quality metrics measuring palliative care outcomes will provide reassurance and guidance to address reservations about the convergence of the two seemingly opposite realities.
A modest proposal
We propose that palliative care be presented to the entire spectrum of transplantation care: on the ward, in the ICU, and after transplantation. More specific “triggers” for palliative care for referral of transplant patients should be identified. Wentlandt et al.4 have described a promising model for an ambulatory clinic, which provides early, integrated palliative care to patients awaiting and receiving organ transplantation. In addition, we propose an application for grant funding for a conference and eventual formation of a work group of transplant surgeons and team members, palliative care clinicians, and patient/families who have experienced one of the aspects of the transplant spectrum. We await the subspecialty certification in hospice and palliative medicine of a transplant surgeon. Outside of transplantation, every other surgical specialty in the United States has diplomates certified in hospice and palliative medicine. We await the benefits that will accrue from research about the merging of these fields.
1. Molmenti EP, Dunn GP: Transplantation and palliative care: The convergence of two seemingly opposite realities. Surg Clin North Am. 2005;85:373-82.
2. Cook D, Rocker G. Dying with dignity in the intensive care unit. N Engl J Med. 2014;370:2506-14.
3. Lamba S, Murphy P, McVicker S, Smith JH, and Mosenthal AC. Changing end-of-life care practice for liver transplant patients: structured palliative care intervention in the surgical intensive care unit. J Pain Symptom Manage. 2012; 44(4):508-19.
4. Wentlandt, K., Dall’Osto, A., Freeman, N., Le, L. W., Kaya, E., Ross, H., Singer, L. G., Abbey, S., Clarke, H. and Zimmermann, C. (2016), The Transplant Palliative Care Clinic: An early palliative care model for patients in a transplant program. Clin Transplant. 2016 Nov 4; doi: 10.1111/ctr.12838.
Dr. Azoulay is a transplantation specialist of Assistance Publique – Hôpitaux de Paris, and the University of Paris. Dr. Dunn is medical director of the Palliative Care Consultation Service at the University of Pittsburgh Medical Center Hamot, and vice-chair of the ACS Committee on Surgical Palliative Care.
Over 10 years ago, a challenge was made in a surgical publication for increased collaboration between the fields of transplantation and palliative care.1
Since that time not much progress has been made bringing these fields together in a consistent way that would mutually benefit patients and the specialties. However, other progress has been made, particularly in the field of palliative care, which could brighten the prospects and broaden the opportunities to accomplish collaboration between palliative care and transplantation.
Growth of palliative services
During the past decade there has been a robust proliferation of hospital-based palliative care programs in the United States. In all, 67% of U.S. hospitals with 50 or more beds report palliative care teams, up from 63% in 2011 and 53% in 2008.
Only a decade ago, critical care and palliative care were generally considered mutually exclusive. Evidence is trickling in to suggest that this is no longer the case. Although palliative care was not an integral part of critical care at that time, patients, families, and even practitioners began to demand these services. Cook and Rocker have eloquently advocated the rightful place of palliative care in the ICU.2
Studies in recent years have shown that the integration of palliative care into critical care decreases in length of ICU and hospital stay, decreases costs, enhances patient/family satisfaction, and promotes a more rapid consensus about goals of care, without increasing mortality. The ICU experience to date could be considered a reassuring precedent for transplantation palliative care.
Integration of palliative care with transplantation
Early palliative care intervention has been shown to improve symptom burden and depression scores in end-stage liver disease patients awaiting transplant. In addition, early palliative care consultation in conjunction with cancer treatment has been associated with increased survival in non–small-cell lung cancer patients. It has been demonstrated that early integration of palliative care in the surgical ICU alongside disease-directed curative care can be accomplished without change in mortality, while improving end-of-life practice in liver transplant patients.3
What palliative care can do for transplant patients
What does palliative care mean for the person (and family) awaiting transplantation? For the cirrhotic patient with cachexia, ascites, and encephalopathy, it means access to the services of a team trained in the management of these symptoms. Palliative care teams can also provide psychosocial and spiritual support for patients and families who are intimidated by the complex navigation of the health care system and the existential threat that end-stage organ failure presents to them. Skilled palliative care and services can be the difference between failing and extended life with a higher quality of life for these very sick patients
Resuscitation of a patient, whether through restoration of organ function or interdicting the progression of disease, begins with resuscitation of hope. Nothing achieves this more quickly than amelioration of burdensome symptoms for the patient and family.
The barriers for transplant surgeons and teams referring and incorporating palliative care services in their practices are multiple and profound. The unique dilemma facing the transplant team is to balance the treatment of the failing organ, the treatment of the patient (and family and friends), and the best use of the graft, a precious gift of society.
Palliative surgery has been defined as any invasive procedure in which the main intention is to mitigate physical symptoms in patients with noncurable disease without causing premature death. The very success of transplantation over the past 3 decades has obscured our memory of transplantation as a type of palliative surgery. It is a well-known axiom of reconstructive surgery that the reconstructed site should be compared to what was there, not to “normal.” Even in the current era of improved immunosuppression and posttransplant support services, one could hardly describe even a successful transplant patient’s experience as “normal.” These patients’ lives may be extended and/or enhanced but they need palliative care before, during, and after transplantation. The growing availability of trained palliative care clinicians and teams, the increased familiarity of palliative and end-of-life care to surgical residents and fellows, and quality metrics measuring palliative care outcomes will provide reassurance and guidance to address reservations about the convergence of the two seemingly opposite realities.
A modest proposal
We propose that palliative care be presented to the entire spectrum of transplantation care: on the ward, in the ICU, and after transplantation. More specific “triggers” for palliative care for referral of transplant patients should be identified. Wentlandt et al.4 have described a promising model for an ambulatory clinic, which provides early, integrated palliative care to patients awaiting and receiving organ transplantation. In addition, we propose an application for grant funding for a conference and eventual formation of a work group of transplant surgeons and team members, palliative care clinicians, and patient/families who have experienced one of the aspects of the transplant spectrum. We await the subspecialty certification in hospice and palliative medicine of a transplant surgeon. Outside of transplantation, every other surgical specialty in the United States has diplomates certified in hospice and palliative medicine. We await the benefits that will accrue from research about the merging of these fields.
1. Molmenti EP, Dunn GP: Transplantation and palliative care: The convergence of two seemingly opposite realities. Surg Clin North Am. 2005;85:373-82.
2. Cook D, Rocker G. Dying with dignity in the intensive care unit. N Engl J Med. 2014;370:2506-14.
3. Lamba S, Murphy P, McVicker S, Smith JH, and Mosenthal AC. Changing end-of-life care practice for liver transplant patients: structured palliative care intervention in the surgical intensive care unit. J Pain Symptom Manage. 2012; 44(4):508-19.
4. Wentlandt, K., Dall’Osto, A., Freeman, N., Le, L. W., Kaya, E., Ross, H., Singer, L. G., Abbey, S., Clarke, H. and Zimmermann, C. (2016), The Transplant Palliative Care Clinic: An early palliative care model for patients in a transplant program. Clin Transplant. 2016 Nov 4; doi: 10.1111/ctr.12838.
Dr. Azoulay is a transplantation specialist of Assistance Publique – Hôpitaux de Paris, and the University of Paris. Dr. Dunn is medical director of the Palliative Care Consultation Service at the University of Pittsburgh Medical Center Hamot, and vice-chair of the ACS Committee on Surgical Palliative Care.
Can Rectal Cancer Patients Benefit from Deintensification of Treatment?
New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.
Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.
Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.
However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.
During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:
- Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
- Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
- Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery).
Does Watch and Wait Work?
Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.
Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
Does Selective Omission of Radiotherapy Work?
Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.
Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:
- FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
- FOLFOX plus chemoradiation.
- FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.
Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.
The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.
“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.
PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
Does Dropping Everything But Immunotherapy Work?
Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.
This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”
What are the Clinical Implications and Next Steps?
Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.
Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.
“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.
Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?
The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.
“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.
“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.
The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”
Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.
The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said.
However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.
“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.
“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.
Dr. Willett and Dr. Benson had no financial conflicts to disclose.
New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.
Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.
Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.
However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.
During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:
- Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
- Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
- Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery).
Does Watch and Wait Work?
Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.
Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
Does Selective Omission of Radiotherapy Work?
Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.
Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:
- FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
- FOLFOX plus chemoradiation.
- FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.
Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.
The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.
“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.
PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
Does Dropping Everything But Immunotherapy Work?
Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.
This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”
What are the Clinical Implications and Next Steps?
Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.
Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.
“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.
Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?
The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.
“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.
“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.
The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”
Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.
The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said.
However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.
“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.
“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.
Dr. Willett and Dr. Benson had no financial conflicts to disclose.
New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.
Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.
Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.
However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.
During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:
- Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
- Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
- Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery).
Does Watch and Wait Work?
Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.
Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
Does Selective Omission of Radiotherapy Work?
Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.
Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:
- FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
- FOLFOX plus chemoradiation.
- FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.
Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.
The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.
“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.
PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
Does Dropping Everything But Immunotherapy Work?
Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.
This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”
What are the Clinical Implications and Next Steps?
Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.
Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.
“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.
Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?
The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.
“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.
“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.
The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”
Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.
The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said.
However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.
“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.
“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.
Dr. Willett and Dr. Benson had no financial conflicts to disclose.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167837</fileName> <TBEID>0C04FC82.SIG</TBEID> <TBUniqueIdentifier>MD_0C04FC82</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>NCCN rectal cancer v4</storyname> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240425T151436</QCDate> <firstPublished>20240425T151455</firstPublished> <LastPublished>20240425T151455</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240425T151455</CMSDate> <articleSource>FROM NCCN 2024</articleSource> <facebookInfo/> <meetingNumber>5291-24</meetingNumber> <byline>Heidi Splete</byline> <bylineText>HEIDI SPLETE</bylineText> <bylineFull>HEIDI SPLETE</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of </metaDescription> <articlePDF/> <teaserImage/> <teaser>An expert at the National Comprehensive Cancer Network annual conference discussed treatment-sparing strategies for eligible patients.</teaser> <title>Can Rectal Cancer Patients Benefit from Deintensification of Treatment?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>GIHOLD</publicationCode> <pubIssueName>January 2014</pubIssueName> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> </publications> <sections> <term>27980</term> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term>213</term> <term canonical="true">67020</term> <term>270</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Can Rectal Cancer Patients Benefit from Deintensification of Treatment?</title> <deck/> </itemMeta> <itemContent> <p>New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.</p> <p>Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said. <br/><br/>Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.</p> <p>However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.<br/><br/>During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer: </p> <ul class="body"> <li>Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.</li> <li>Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.</li> <li>Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery). </li> </ul> <h2>Does Watch and Wait Work?</h2> <p>Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.</p> <p>Data from the <span class="Hyperlink"><a href="https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3520">OPRA</a></span> trial published in the <em>Journal of Clinical Oncology</em> showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said. <br/><br/></p> <h2> Does Selective Omission of Radiotherapy Work? </h2> <p>Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.</p> <p>Data from the <span class="Hyperlink"><a href="https://ascopubs.org/doi/10.1200/JCO.18.02309?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub 0pubmed">FOWARC trial,</a></span> published in the <em>Journal of Clinical Oncology</em> in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms: </p> <ul class="body"> <li>FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).</li> <li>FOLFOX plus chemoradiation. </li> <li>FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.</li> </ul> <p>Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.<br/><br/>The larger <span class="Hyperlink"><a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2303269">PROSPECT study</a></span> published in <em>The New England Journal of Medicine</em> in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response. <br/><br/>“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said. <br/><br/>PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.<br/><br/></p> <h2> Does Dropping Everything But Immunotherapy Work? </h2> <p>Research is very preliminary, but a small <span class="Hyperlink"><a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2201445">study</a></span> of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in <em>The New England Journal of Medicine</em> “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.</p> <p>This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”</p> <h2>What are the Clinical Implications and Next Steps? </h2> <p>Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.</p> <p>Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued. </p> <p>“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.<br/><br/>Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said. <br/><br/></p> <h2>What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?</h2> <p>The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.</p> <p>“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.<br/><br/>“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago. <br/><br/>The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.” <br/><br/>Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized. <br/><br/>The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said. <br/><br/>However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.<br/><br/>“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added. <br/><br/>“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.<br/><br/>Dr. Willett and Dr. Benson had no financial conflicts to disclose.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM NCCN 2024
Are Direct-to-Consumer Microbiome Tests Clinically Useful?
Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.
“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.
The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
Clinical Implications, Not Applications
The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.
Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.
But , Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.
“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”
Dr. von Rosenvinge and colleagues authored a recent article in Science arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
Unreliable, Unregulated
The lack of reliability has been shown by experts who have tested the tests.
“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”
Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.
“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).
Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.
The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.
“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.
Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:
- Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
- Gaining insight into the interactions among the identified pathogens.
- Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
- Creating a prototype formulation for testing.
- Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
- Conducting clinical testing.
Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
Potential Pitfalls
Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”
“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”
Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.
“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.
Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
What to Tell Patients
“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.
“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”
Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”
When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.
“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”
Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”
She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
Educate Clinicians, Companies
More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.
“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.
“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.
As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”
Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.
“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.
Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.
A version of this article appeared on Medscape.com.
Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.
“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.
The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
Clinical Implications, Not Applications
The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.
Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.
But , Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.
“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”
Dr. von Rosenvinge and colleagues authored a recent article in Science arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
Unreliable, Unregulated
The lack of reliability has been shown by experts who have tested the tests.
“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”
Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.
“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).
Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.
The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.
“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.
Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:
- Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
- Gaining insight into the interactions among the identified pathogens.
- Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
- Creating a prototype formulation for testing.
- Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
- Conducting clinical testing.
Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
Potential Pitfalls
Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”
“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”
Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.
“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.
Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
What to Tell Patients
“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.
“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”
Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”
When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.
“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”
Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”
She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
Educate Clinicians, Companies
More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.
“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.
“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.
As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”
Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.
“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.
Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.
A version of this article appeared on Medscape.com.
Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.
“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.
The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
Clinical Implications, Not Applications
The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.
Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.
But , Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.
“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”
Dr. von Rosenvinge and colleagues authored a recent article in Science arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
Unreliable, Unregulated
The lack of reliability has been shown by experts who have tested the tests.
“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”
Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.
“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).
Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.
The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.
“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.
Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:
- Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
- Gaining insight into the interactions among the identified pathogens.
- Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
- Creating a prototype formulation for testing.
- Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
- Conducting clinical testing.
Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
Potential Pitfalls
Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”
“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”
Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.
“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.
Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
What to Tell Patients
“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.
“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”
Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”
When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.
“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”
Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”
She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
Educate Clinicians, Companies
More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.
“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.
“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.
As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”
Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.
“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.
Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.
A version of this article appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167843</fileName> <TBEID>0C04FCA0.SIG</TBEID> <TBUniqueIdentifier>MD_0C04FCA0</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240425T140211</QCDate> <firstPublished>20240425T140221</firstPublished> <LastPublished>20240425T140221</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240425T140221</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>M Larkin</byline> <bylineText>MARILYNN LARKIN</bylineText> <bylineFull>MARILYNN LARKIN</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>Feature</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>lack of scientific evidence and validity hasn’t stopped a growing number of companies across the globe from offering direct-to-consumer (DTC) microbiome tests</metaDescription> <articlePDF/> <teaserImage>170850</teaserImage> <teaser>The lack of reliability has been shown by experts who have tested the tests.</teaser> <title>Are Direct-to-Consumer Microbiome Tests Clinically Useful?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>GIHOLD</publicationCode> <pubIssueName>January 2014</pubIssueName> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> </publications_g> <publications> <term canonical="true">21</term> <term>15</term> <term>26</term> </publications> <sections> <term canonical="true">27980</term> <term>39313</term> </sections> <topics> <term canonical="true">213</term> <term>49620</term> <term>38029</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240060cc.jpg</altRep> <description role="drol:caption">Dr. Colleen R. Kelly</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Are Direct-to-Consumer Microbiome Tests Clinically Useful?</title> <deck/> </itemMeta> <itemContent> <p>Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.</p> <p>“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.<br/><br/>The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.<br/><br/></p> <h2>Clinical Implications, Not Applications</h2> <p>The microbiome is the “<span class="Hyperlink"><a href="http://constellation of microorganisms">constellation of microorganisms</a> </span>that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some <span class="Hyperlink"><a href="https://www.sciencefocus.com/the-human-body/human-microbiome">39 trillion cells</a></span>.</p> <p>Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the <span class="Hyperlink"><a href="https://www.nature.com/articles/s41598-023-30625-9">most studied</a>.</span> However, while research is increasingly demonstrating that the gut microbiome has <span class="Hyperlink"><a href="https://doi.org/10.3390/biomedicines12010194">clinical implications</a></span>, much work needs to be done before reliable applications based on that research are available.<br/><br/>But <span class="tag metaDescription">lack of scientific evidence and validity hasn’t stopped a growing number of companies across the globe from offering direct-to-consumer (DTC) microbiome tests</span>, Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.<br/><br/>“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”<br/><br/>Dr. von Rosenvinge and colleagues authored a <span class="Hyperlink"><a href="https://doi.org/10.1126/science.adk4271">recent article</a></span> in <em>Science</em> arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified <span class="Hyperlink"><a href="https://www.law.umaryland.edu/media/sol/sol-2022-images-and-files/academics/programs-and-centers/health-law-program/pdfs-docs-and-files/DTC-Microbiome-Testing-Companies---Tables-Updated-2-26-24.pdf">31 companies</a></span> globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.<br/><br/></p> <h2>Unreliable, Unregulated</h2> <p>The lack of reliability has been shown by experts who have tested the tests.</p> <p>“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”<br/><br/>Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.<br/><br/>“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent <span class="Hyperlink"><a href="https://www.gutmicrobiotaforhealth.com/washington-2024/">Gut Microbiota for Health World Summit</a></span>.<br/><br/>Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.<br/><br/>The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.<br/><br/>“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of <span class="Hyperlink"><a href="https://www.biohmhealth.com/">BIOHM</a></span>, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is <span class="Hyperlink"><a href="https://www.law.umaryland.edu/media/sol/sol-2022-images-and-files/academics/programs-and-centers/health-law-program/pdfs-docs-and-files/DTC-Microbiome-Testing-Companies---Tables-Updated-2-26-24.pdf">one of the 31 companies</a></span> identified by Dr. von Rosenvinge and colleagues, as noted above.<br/><br/>Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues <span class="Hyperlink"><a href="https://www.gastrojournal.org/article/S0016-5085(23)00049-5/fulltext">described such an approach</a></span> by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using <span class="Hyperlink">Crohn’s disease</span> as a model. Their strategy involved the following steps:</p> <ul class="body"> <li>Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.</li> <li>Gaining insight into the interactions among the identified pathogens.</li> <li>Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.</li> <li>Creating a prototype formulation for testing.</li> <li>Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.</li> <li>Conducting clinical testing.</li> </ul> <p>Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”<br/><br/></p> <h2>Potential Pitfalls</h2> <p>Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”</p> <p>“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”<br/><br/>Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.<br/><br/>“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.<br/><br/>Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as <span class="Hyperlink">colon cancer</span>, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.<br/><br/></p> <h2>What to Tell Patients</h2> <p>“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.[[{"fid":"170850","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Colleen R. Kelly, Brigham and Women’s Hospital, Boston","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Colleen R. Kelly"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]</p> <p>“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in <span class="Hyperlink">irritable bowel syndrome</span>.”<br/><br/>Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”<br/><br/>When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.<br/><br/>“Our <span class="Hyperlink"><a href="https://www.law.umaryland.edu/media/sol/sol-2022-images-and-files/academics/programs-and-centers/health-law-program/pdfs-docs-and-files/Microbiome-Tested-and-Untested-Consumers-Focus-Group-Report.pdf">patient focus groups</a></span> suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”<br/><br/>Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”<br/><br/>She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.<br/><br/></p> <h2>Educate Clinicians, Companies</h2> <p>More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.</p> <p>“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.<br/><br/>“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.<br/><br/>As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”<br/><br/>Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.<br/><br/>“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.<br/><br/>Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/are-direct-consumer-microbiome-tests-clinically-useful-2024a10007yy">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Federal Trade Commission Bans Noncompete Agreements, Urges More Protections for Healthcare Workers
But business groups have vowed to challenge the decision in court.
The proposed final rule passed on a 3-2 vote, with the dissenting commissioners disputing the FTC’s authority to broadly ban noncompetes.
Tensions around noncompetes have been building for years. In 2021, President Biden issued an executive order supporting measures to improve economic competition, in which he urged the FTC to consider its rulemaking authority to address noncompete clauses that unfairly limit workers’ mobility. In January 2023, per that directive, the agency proposed ending the restrictive covenants.
While the FTC estimates that the final rule will reduce healthcare costs by up to $194 billion over the next decade and increase worker earnings by $300 million annually, the ruling faces legal hurdles.
US Chamber of Commerce president and CEO Suzanne P. Clark said in a statement that the move is a “blatant power grab” that will undermine competitive business practices, adding that the Chamber will sue to block the measure.
The FTC received more than 26,000 comments on noncompetes during the public feedback period, with about 25,000 supporting the measure, said Benjamin Cady, JD, an FTC attorney.
Mr. Cady called the feedback “compelling,” citing instances of workers who were forced to commute long distances, uproot their families, or risk expensive litigation for wanting to pursue job opportunities.
For example, a comment from a physician working in Appalachia highlights the potential real-life implications of the agreements. “With hospital systems merging, providers with aggressive noncompetes must abandon the community that they serve if they [choose] to leave their employer. Healthcare providers feel trapped in their current employment situation, leading to significant burnout that can shorten their [career] longevity.”
Commissioner Alvaro Bedoya said physicians have had their lives upended by cumbersome noncompetes, often having to move out of state to practice. “A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” he said.
It’s unclear whether physicians and others who work for nonprofit healthcare groups or hospitals will be covered by the new ban. FTC Commissioner Rebecca Slaughter acknowledged that the agency’s jurisdictional limitations mean that employees of “certain nonprofit organizations” may not benefit from the rule.
“We want to be transparent about the limitation and recognize there are workers, especially healthcare workers, who are bound by anticompetitive and unfair noncompete clauses, that our rule will struggle to reach,” she said. To cover nonprofit healthcare employees, Ms. Slaughter urged Congress to pass legislation banning noncompetes, such as the Workforce Mobility Act of 2021 and the Freedom to Compete Act of 2023.
The FTC final rule will take effect 120 days after it is published in the federal register, and new noncompete agreements will be banned as of this date. However, existing contracts for senior executives will remain in effect because these individuals are less likely to experience “acute harm” due to their ability to negotiate accordingly, said Mr. Cady.
States, AMA Take Aim at Noncompetes
Before the federal ban, several states had already passed legislation limiting the reach of noncompetes. According to a recent article in the Journal of the American College of Cardiology, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota.
The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually.
Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause.
Rachel Marcus, MD, a cardiologist in Washington, DC, found out how limiting her employment contract’s noncompete clause was when she wanted to leave a former position. Due to the restrictions, she told this news organization that she couldn’t work locally for a competitor for 2 years. The closest location she could seek employment without violating the agreement was Baltimore, approximately 40 miles away.
Dr. Marcus ultimately moved to another position within the same organization because of the company’s reputation for being “aggressive” in their enforcement actions.
Although the American Medical Association (AMA) does not support a total ban, its House of Delegates adopted policies last year to support the prohibition of noncompete contracts for physicians employed by for-profit or nonprofit hospitals, hospital systems, or staffing companies.
Challenges Await
The American Hospital Association, which opposed the proposed rule, called it “bad policy.” The decision “will likely be short-lived, with courts almost certain to stop it before it can do damage to hospitals’ ability to care for their patients and communities,” the association said in a statement.
To ease the transition to the new rule, the FTC also released a model language for employers to use when discussing the changes with their employees. “All employers need to do to comply with the rule is to stop enforcing existing noncompetes with workers other than senior executives and provide notice to such workers,” he said.
Dr. Marcus hopes the ban improves doctors’ lives. “Your employer is going to have to treat you better because they know that you can easily go across town to a place that has a higher salary, and your patient can go with you.”
A version of this article appeared on Medscape.com.
But business groups have vowed to challenge the decision in court.
The proposed final rule passed on a 3-2 vote, with the dissenting commissioners disputing the FTC’s authority to broadly ban noncompetes.
Tensions around noncompetes have been building for years. In 2021, President Biden issued an executive order supporting measures to improve economic competition, in which he urged the FTC to consider its rulemaking authority to address noncompete clauses that unfairly limit workers’ mobility. In January 2023, per that directive, the agency proposed ending the restrictive covenants.
While the FTC estimates that the final rule will reduce healthcare costs by up to $194 billion over the next decade and increase worker earnings by $300 million annually, the ruling faces legal hurdles.
US Chamber of Commerce president and CEO Suzanne P. Clark said in a statement that the move is a “blatant power grab” that will undermine competitive business practices, adding that the Chamber will sue to block the measure.
The FTC received more than 26,000 comments on noncompetes during the public feedback period, with about 25,000 supporting the measure, said Benjamin Cady, JD, an FTC attorney.
Mr. Cady called the feedback “compelling,” citing instances of workers who were forced to commute long distances, uproot their families, or risk expensive litigation for wanting to pursue job opportunities.
For example, a comment from a physician working in Appalachia highlights the potential real-life implications of the agreements. “With hospital systems merging, providers with aggressive noncompetes must abandon the community that they serve if they [choose] to leave their employer. Healthcare providers feel trapped in their current employment situation, leading to significant burnout that can shorten their [career] longevity.”
Commissioner Alvaro Bedoya said physicians have had their lives upended by cumbersome noncompetes, often having to move out of state to practice. “A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” he said.
It’s unclear whether physicians and others who work for nonprofit healthcare groups or hospitals will be covered by the new ban. FTC Commissioner Rebecca Slaughter acknowledged that the agency’s jurisdictional limitations mean that employees of “certain nonprofit organizations” may not benefit from the rule.
“We want to be transparent about the limitation and recognize there are workers, especially healthcare workers, who are bound by anticompetitive and unfair noncompete clauses, that our rule will struggle to reach,” she said. To cover nonprofit healthcare employees, Ms. Slaughter urged Congress to pass legislation banning noncompetes, such as the Workforce Mobility Act of 2021 and the Freedom to Compete Act of 2023.
The FTC final rule will take effect 120 days after it is published in the federal register, and new noncompete agreements will be banned as of this date. However, existing contracts for senior executives will remain in effect because these individuals are less likely to experience “acute harm” due to their ability to negotiate accordingly, said Mr. Cady.
States, AMA Take Aim at Noncompetes
Before the federal ban, several states had already passed legislation limiting the reach of noncompetes. According to a recent article in the Journal of the American College of Cardiology, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota.
The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually.
Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause.
Rachel Marcus, MD, a cardiologist in Washington, DC, found out how limiting her employment contract’s noncompete clause was when she wanted to leave a former position. Due to the restrictions, she told this news organization that she couldn’t work locally for a competitor for 2 years. The closest location she could seek employment without violating the agreement was Baltimore, approximately 40 miles away.
Dr. Marcus ultimately moved to another position within the same organization because of the company’s reputation for being “aggressive” in their enforcement actions.
Although the American Medical Association (AMA) does not support a total ban, its House of Delegates adopted policies last year to support the prohibition of noncompete contracts for physicians employed by for-profit or nonprofit hospitals, hospital systems, or staffing companies.
Challenges Await
The American Hospital Association, which opposed the proposed rule, called it “bad policy.” The decision “will likely be short-lived, with courts almost certain to stop it before it can do damage to hospitals’ ability to care for their patients and communities,” the association said in a statement.
To ease the transition to the new rule, the FTC also released a model language for employers to use when discussing the changes with their employees. “All employers need to do to comply with the rule is to stop enforcing existing noncompetes with workers other than senior executives and provide notice to such workers,” he said.
Dr. Marcus hopes the ban improves doctors’ lives. “Your employer is going to have to treat you better because they know that you can easily go across town to a place that has a higher salary, and your patient can go with you.”
A version of this article appeared on Medscape.com.
But business groups have vowed to challenge the decision in court.
The proposed final rule passed on a 3-2 vote, with the dissenting commissioners disputing the FTC’s authority to broadly ban noncompetes.
Tensions around noncompetes have been building for years. In 2021, President Biden issued an executive order supporting measures to improve economic competition, in which he urged the FTC to consider its rulemaking authority to address noncompete clauses that unfairly limit workers’ mobility. In January 2023, per that directive, the agency proposed ending the restrictive covenants.
While the FTC estimates that the final rule will reduce healthcare costs by up to $194 billion over the next decade and increase worker earnings by $300 million annually, the ruling faces legal hurdles.
US Chamber of Commerce president and CEO Suzanne P. Clark said in a statement that the move is a “blatant power grab” that will undermine competitive business practices, adding that the Chamber will sue to block the measure.
The FTC received more than 26,000 comments on noncompetes during the public feedback period, with about 25,000 supporting the measure, said Benjamin Cady, JD, an FTC attorney.
Mr. Cady called the feedback “compelling,” citing instances of workers who were forced to commute long distances, uproot their families, or risk expensive litigation for wanting to pursue job opportunities.
For example, a comment from a physician working in Appalachia highlights the potential real-life implications of the agreements. “With hospital systems merging, providers with aggressive noncompetes must abandon the community that they serve if they [choose] to leave their employer. Healthcare providers feel trapped in their current employment situation, leading to significant burnout that can shorten their [career] longevity.”
Commissioner Alvaro Bedoya said physicians have had their lives upended by cumbersome noncompetes, often having to move out of state to practice. “A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” he said.
It’s unclear whether physicians and others who work for nonprofit healthcare groups or hospitals will be covered by the new ban. FTC Commissioner Rebecca Slaughter acknowledged that the agency’s jurisdictional limitations mean that employees of “certain nonprofit organizations” may not benefit from the rule.
“We want to be transparent about the limitation and recognize there are workers, especially healthcare workers, who are bound by anticompetitive and unfair noncompete clauses, that our rule will struggle to reach,” she said. To cover nonprofit healthcare employees, Ms. Slaughter urged Congress to pass legislation banning noncompetes, such as the Workforce Mobility Act of 2021 and the Freedom to Compete Act of 2023.
The FTC final rule will take effect 120 days after it is published in the federal register, and new noncompete agreements will be banned as of this date. However, existing contracts for senior executives will remain in effect because these individuals are less likely to experience “acute harm” due to their ability to negotiate accordingly, said Mr. Cady.
States, AMA Take Aim at Noncompetes
Before the federal ban, several states had already passed legislation limiting the reach of noncompetes. According to a recent article in the Journal of the American College of Cardiology, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota.
The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually.
Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause.
Rachel Marcus, MD, a cardiologist in Washington, DC, found out how limiting her employment contract’s noncompete clause was when she wanted to leave a former position. Due to the restrictions, she told this news organization that she couldn’t work locally for a competitor for 2 years. The closest location she could seek employment without violating the agreement was Baltimore, approximately 40 miles away.
Dr. Marcus ultimately moved to another position within the same organization because of the company’s reputation for being “aggressive” in their enforcement actions.
Although the American Medical Association (AMA) does not support a total ban, its House of Delegates adopted policies last year to support the prohibition of noncompete contracts for physicians employed by for-profit or nonprofit hospitals, hospital systems, or staffing companies.
Challenges Await
The American Hospital Association, which opposed the proposed rule, called it “bad policy.” The decision “will likely be short-lived, with courts almost certain to stop it before it can do damage to hospitals’ ability to care for their patients and communities,” the association said in a statement.
To ease the transition to the new rule, the FTC also released a model language for employers to use when discussing the changes with their employees. “All employers need to do to comply with the rule is to stop enforcing existing noncompetes with workers other than senior executives and provide notice to such workers,” he said.
Dr. Marcus hopes the ban improves doctors’ lives. “Your employer is going to have to treat you better because they know that you can easily go across town to a place that has a higher salary, and your patient can go with you.”
A version of this article appeared on Medscape.com.
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This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The Federal Trade Commission (FTC) voted Tuesday to ban noncompete agreements, possibly making it easier for doctors to switch employers without having to leave</metaDescription> <articlePDF/> <teaserImage/> <teaser>But dissenting commissioners dispute the FTC’s authority to broadly ban noncompetes.</teaser> <title>Federal Trade Commission Bans Noncompete Agreements, Urges More Protections for Healthcare Workers</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> 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</topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Federal Trade Commission Bans Noncompete Agreements, Urges More Protections for Healthcare Workers</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">The Federal Trade Commission (FTC) voted Tuesday to ban noncompete agreements, possibly making it easier for doctors to switch employers without having to leave their communities and patients behind.</span> But business groups have vowed to challenge the decision in court.</p> <p>The <span class="Hyperlink"><a href="https://www.ftc.gov/news-events/news/press-releases/2024/04/ftc-announces-rule-banning-noncompetes">proposed final rule</a></span> passed on a 3-2 vote, with the dissenting commissioners disputing the FTC’s authority to broadly ban noncompetes.<br/><br/>Tensions around noncompetes have been building for years. In 2021, President Biden issued an <span class="Hyperlink"><a href="https://www.whitehouse.gov/briefing-room/presidential-actions/2021/07/09/executive-order-on-promoting-competition-in-the-american-economy/">executive order</a></span> supporting measures to improve economic competition, in which he urged the FTC to consider its rulemaking authority to address noncompete clauses that unfairly limit workers’ mobility. In January 2023, per that directive, the agency <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/986904">proposed ending the restrictive covenants</a></span>.<br/><br/>While the FTC estimates that the final rule will reduce healthcare costs by up to $194 billion over the next decade and increase worker earnings by $300 million annually, the ruling faces legal hurdles.<br/><br/>US Chamber of Commerce president and CEO Suzanne P. Clark said in a <span class="Hyperlink"><a href="https://www.uschamber.com/finance/antitrust/u-s-chamber-to-sue-ftc-over-unlawful-power-grab-on-noncompete-agreements-ban">statement</a></span> that the move is a “blatant power grab” that will undermine competitive business practices, adding that the Chamber will sue to block the measure.<br/><br/>The FTC received more than 26,000 comments on noncompetes during the public feedback period, with about 25,000 supporting the measure, said Benjamin Cady, JD, an FTC attorney.<br/><br/>Mr. Cady called the feedback “compelling,” citing instances of workers who were forced to commute long distances, uproot their families, or <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/urologist-sues-health-system-over-noncompete-clause-2024a1000389">risk expensive litigation</a></span> for wanting to pursue job opportunities.<br/><br/>For example, a comment from a physician working in Appalachia highlights the potential real-life implications of the agreements. “With <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/hospital-mergers-2024-five-things-know-2024a100047m">hospital systems merging</a></span>, providers with aggressive noncompetes must abandon the community that they serve if they [choose] to leave their employer. Healthcare providers feel trapped in their current employment situation, leading to <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/some-mds-long-covid-burnout-new-reality-2024a10006hq">significant burnout</a></span> that can shorten their [career] longevity.”<br/><br/>Commissioner Alvaro Bedoya said physicians have had their <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/989694">lives upended</a></span> by cumbersome noncompetes, often having to move out of state to practice. “A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” he said.<br/><br/>It’s unclear whether physicians and others who work for nonprofit healthcare groups or hospitals will be covered by the new ban. FTC Commissioner Rebecca Slaughter acknowledged that the agency’s jurisdictional limitations mean that employees of “certain nonprofit organizations” may not benefit from the rule.<br/><br/>“We want to be transparent about the limitation and recognize there are workers, especially healthcare workers, who are bound by anticompetitive and unfair noncompete clauses, that our rule will struggle to reach,” she said. To cover nonprofit healthcare employees, Ms. Slaughter urged Congress to pass legislation banning noncompetes, such as the <span class="Hyperlink"><a href="https://www.congress.gov/bill/117th-congress/senate-bill/483">Workforce Mobility Act of 2021</a></span> and the <span class="Hyperlink"><a href="https://www.congress.gov/bill/118th-congress/senate-bill/379">Freedom to Compete Act of 2023</a></span>.<br/><br/>The FTC final rule will take effect 120 days after it is published in the federal register, and new noncompete agreements will be banned as of this date. However, existing contracts for senior executives will remain in effect because these individuals are less likely to experience “acute harm” due to their ability to negotiate accordingly, said Mr. Cady.<br/><br/></p> <h2>States, AMA Take Aim at Noncompetes</h2> <p>Before the federal ban, several states had already passed legislation limiting the reach of noncompetes. According to a recent article in the <em>Journal of the American College of Cardiology</em>, <span class="Hyperlink"><a href="https://www.jacc.org/doi/10.1016/j.jacadv.2023.100547">12 states</a></span> prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota.<br/><br/>The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in <span class="Hyperlink"><a href="https://www.oregon.gov/boli/employers/pages/noncompetition-agreements.aspx">Oregon</a></span>, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits <span class="Hyperlink"><a href="https://oag.dc.gov/blog/worker-alert-noncompete-provisions-are-now-illegal">2-year noncompetes</a></span> for “medical specialists” earning over $250,000 annually.<br/><br/>Indiana employers can no longer enter into noncompete agreements with <span class="Hyperlink"><a href="https://iga.in.gov/legislative/2023/bills/senate/7/details">primary care providers</a></span>. Other specialties may be subject to the clauses, except when the physician <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/994478">terminates the contract for cause</a></span> or when an employer terminates the contract without cause.<br/><br/>Rachel Marcus, MD, a cardiologist in Washington, DC, found out how limiting her employment contract’s noncompete clause was when she wanted to leave a former position. Due to the restrictions, she told this news organization that she couldn’t work locally for a competitor for 2 years. The closest location she could seek employment without violating the agreement was Baltimore, approximately 40 miles away.<br/><br/>Dr. Marcus ultimately moved to another position within the same organization because of the company’s reputation for being “aggressive” in their enforcement actions.<br/><br/>Although the American Medical Association (AMA) does not support a total ban, its House of Delegates <span class="Hyperlink"><a href="https://www.ama-assn.org/medical-residents/transition-resident-attending/ama-backs-effort-ban-many-physician-noncompete">adopted policies</a></span> last year to support the prohibition of noncompete contracts for physicians employed by for-profit or nonprofit hospitals, hospital systems, or staffing companies.<br/><br/></p> <h2>Challenges Await</h2> <p>The American Hospital Association, which opposed the proposed rule, called it “bad policy.” The decision “will likely be short-lived, with courts almost certain to stop it before it can do damage to hospitals’ ability to care for their patients and communities,” the association said in a <span class="Hyperlink"><a href="https://www.aha.org/press-releases/2024-04-23-aha-statement-final-ftc-noncompete-regulation">statement</a></span>.<br/><br/>To ease the transition to the new rule, the FTC also released a <span class="Hyperlink"><a href="https://www.ftc.gov/legal-library/browse/rules/noncompete-rule">model language</a></span> for employers to use when discussing the changes with their employees. “All employers need to do to comply with the rule is to stop enforcing existing noncompetes with workers other than senior executives and provide notice to such workers,” he said.<br/><br/>Dr. Marcus hopes the ban <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/are-you-ready-ai-be-better-doctor-than-you-2024a100070q">improves doctors’ lives</a></span>. “Your employer is going to have to treat you better because they know that you can easily go across town to a place that has a higher salary, and your patient can go with you.”<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/federal-trade-commission-bans-noncompete-agreements-urges-2024a10007y0">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Is Osimertinib Better Alone or With Chemotherapy in Non–Small Cell Lung Cancer?
SAN DIEGO —
That is a question brewing among some oncologists now that the US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso, AstraZeneca) for both indications in patients with epidermal growth factor receptor (EGFR) mutations.
An answer began to emerge in research presented at the American Association for Cancer Research annual meeting.
An exploratory analysis of the FLAURA2 trial found that, when patients have EGFR mutations on baseline circulating tumor DNA (ctDNA) testing, the combination treatment can extend progression-free survival (PFS). In this patient group, those receiving osimertinib alongside pemetrexed plus cisplatin or carboplatin had a 9-month PFS advantage compared with those who received osimertinib alone.
Conversely, when patients do not have EGFR mutations following baseline ctDNA testing, osimertinib alone appears to offer similar PFS outcomes to the combination therapy, but with less toxicity.
“Baseline detection of plasma EGFR mutations may identify a subgroup of patients who derive most benefit from the addition of platinum-pemetrexed to osimertinib as first-line treatment of EGFR-mutated advance non–small cell lung cancer,” investigator Pasi A. Jänne, MD, PhD, a lung cancer oncologist at the Dana-Farber Cancer Institute, Boston, said during his presentation.
The FLAURA2 trial randomized 557 patients equally to daily osimertinib either alone or with pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by pemetrexed every 3 weeks until disease progression or unacceptable toxicity.
Patients were tested for Ex19del or L858R EGFR mutations at baseline and at 3 and 6 weeks; baseline mutations were found in 73% of evaluable patients.
In patients with baseline mutations, the median PFS was 24.8 months with the combination therapy vs 13.9 months with osimertinib alone (hazard ratio [HR], 0.60).
In patients without baseline mutations, the median PFS was similar in both groups — 33.3 months with the combination vs 30.3 months with monotherapy (HR, 0.93; 95% CI, 0.51-1.72).
The investigators also found that having baseline mutations was associated with worse outcomes regardless of study arm, and mutation clearance was associated with improved outcomes. Clearance occurred more quickly among patients receiving the combination treatment, but almost 90% of patients in both arms cleared their mutations by week 6.
“As we move forward and think about which of our patients we would treat with the combination ... the presence of baseline EGFR mutations in ctDNA may be one of the features that goes into the conversation,” Dr. Jänne said.
Study discussant Marina Chiara Garassino, MD, a thoracic oncologist at the University of Chicago, agreed that this trial can help oncologists make this kind of treatment decision.
Patients with baseline EGFR mutations also tended to have larger tumors, more brain metastases, and worse performance scores; the combination therapy makes sense when such factors are present in patients with baseline EGFR mutations, Dr. Garassino said.
The wrinkle in the findings is that the study used digital droplet polymerase chain reaction (Biodesix) to test for EGFR mutations, which is not commonly used. Clinicians often use next-generation sequencing, which is less sensitive and can lead to false negatives.
It makes it difficult to know how to apply the findings to everyday practice, but Janne hopes a study will be done to correlate next-generation sequencing detection with outcomes.
The study was funded by AstraZeneca, maker of osimertinib, and researchers included AstraZeneca employees. Dr. Jänne is a consultant for and reported research funding from the company. He is a co-inventor on an EGFR mutations patent. Dr. Garassino is also an AstraZeneca consultant and reported institutional financial interests in the company.
A version of this article appeared on Medscape.com.
SAN DIEGO —
That is a question brewing among some oncologists now that the US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso, AstraZeneca) for both indications in patients with epidermal growth factor receptor (EGFR) mutations.
An answer began to emerge in research presented at the American Association for Cancer Research annual meeting.
An exploratory analysis of the FLAURA2 trial found that, when patients have EGFR mutations on baseline circulating tumor DNA (ctDNA) testing, the combination treatment can extend progression-free survival (PFS). In this patient group, those receiving osimertinib alongside pemetrexed plus cisplatin or carboplatin had a 9-month PFS advantage compared with those who received osimertinib alone.
Conversely, when patients do not have EGFR mutations following baseline ctDNA testing, osimertinib alone appears to offer similar PFS outcomes to the combination therapy, but with less toxicity.
“Baseline detection of plasma EGFR mutations may identify a subgroup of patients who derive most benefit from the addition of platinum-pemetrexed to osimertinib as first-line treatment of EGFR-mutated advance non–small cell lung cancer,” investigator Pasi A. Jänne, MD, PhD, a lung cancer oncologist at the Dana-Farber Cancer Institute, Boston, said during his presentation.
The FLAURA2 trial randomized 557 patients equally to daily osimertinib either alone or with pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by pemetrexed every 3 weeks until disease progression or unacceptable toxicity.
Patients were tested for Ex19del or L858R EGFR mutations at baseline and at 3 and 6 weeks; baseline mutations were found in 73% of evaluable patients.
In patients with baseline mutations, the median PFS was 24.8 months with the combination therapy vs 13.9 months with osimertinib alone (hazard ratio [HR], 0.60).
In patients without baseline mutations, the median PFS was similar in both groups — 33.3 months with the combination vs 30.3 months with monotherapy (HR, 0.93; 95% CI, 0.51-1.72).
The investigators also found that having baseline mutations was associated with worse outcomes regardless of study arm, and mutation clearance was associated with improved outcomes. Clearance occurred more quickly among patients receiving the combination treatment, but almost 90% of patients in both arms cleared their mutations by week 6.
“As we move forward and think about which of our patients we would treat with the combination ... the presence of baseline EGFR mutations in ctDNA may be one of the features that goes into the conversation,” Dr. Jänne said.
Study discussant Marina Chiara Garassino, MD, a thoracic oncologist at the University of Chicago, agreed that this trial can help oncologists make this kind of treatment decision.
Patients with baseline EGFR mutations also tended to have larger tumors, more brain metastases, and worse performance scores; the combination therapy makes sense when such factors are present in patients with baseline EGFR mutations, Dr. Garassino said.
The wrinkle in the findings is that the study used digital droplet polymerase chain reaction (Biodesix) to test for EGFR mutations, which is not commonly used. Clinicians often use next-generation sequencing, which is less sensitive and can lead to false negatives.
It makes it difficult to know how to apply the findings to everyday practice, but Janne hopes a study will be done to correlate next-generation sequencing detection with outcomes.
The study was funded by AstraZeneca, maker of osimertinib, and researchers included AstraZeneca employees. Dr. Jänne is a consultant for and reported research funding from the company. He is a co-inventor on an EGFR mutations patent. Dr. Garassino is also an AstraZeneca consultant and reported institutional financial interests in the company.
A version of this article appeared on Medscape.com.
SAN DIEGO —
That is a question brewing among some oncologists now that the US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso, AstraZeneca) for both indications in patients with epidermal growth factor receptor (EGFR) mutations.
An answer began to emerge in research presented at the American Association for Cancer Research annual meeting.
An exploratory analysis of the FLAURA2 trial found that, when patients have EGFR mutations on baseline circulating tumor DNA (ctDNA) testing, the combination treatment can extend progression-free survival (PFS). In this patient group, those receiving osimertinib alongside pemetrexed plus cisplatin or carboplatin had a 9-month PFS advantage compared with those who received osimertinib alone.
Conversely, when patients do not have EGFR mutations following baseline ctDNA testing, osimertinib alone appears to offer similar PFS outcomes to the combination therapy, but with less toxicity.
“Baseline detection of plasma EGFR mutations may identify a subgroup of patients who derive most benefit from the addition of platinum-pemetrexed to osimertinib as first-line treatment of EGFR-mutated advance non–small cell lung cancer,” investigator Pasi A. Jänne, MD, PhD, a lung cancer oncologist at the Dana-Farber Cancer Institute, Boston, said during his presentation.
The FLAURA2 trial randomized 557 patients equally to daily osimertinib either alone or with pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by pemetrexed every 3 weeks until disease progression or unacceptable toxicity.
Patients were tested for Ex19del or L858R EGFR mutations at baseline and at 3 and 6 weeks; baseline mutations were found in 73% of evaluable patients.
In patients with baseline mutations, the median PFS was 24.8 months with the combination therapy vs 13.9 months with osimertinib alone (hazard ratio [HR], 0.60).
In patients without baseline mutations, the median PFS was similar in both groups — 33.3 months with the combination vs 30.3 months with monotherapy (HR, 0.93; 95% CI, 0.51-1.72).
The investigators also found that having baseline mutations was associated with worse outcomes regardless of study arm, and mutation clearance was associated with improved outcomes. Clearance occurred more quickly among patients receiving the combination treatment, but almost 90% of patients in both arms cleared their mutations by week 6.
“As we move forward and think about which of our patients we would treat with the combination ... the presence of baseline EGFR mutations in ctDNA may be one of the features that goes into the conversation,” Dr. Jänne said.
Study discussant Marina Chiara Garassino, MD, a thoracic oncologist at the University of Chicago, agreed that this trial can help oncologists make this kind of treatment decision.
Patients with baseline EGFR mutations also tended to have larger tumors, more brain metastases, and worse performance scores; the combination therapy makes sense when such factors are present in patients with baseline EGFR mutations, Dr. Garassino said.
The wrinkle in the findings is that the study used digital droplet polymerase chain reaction (Biodesix) to test for EGFR mutations, which is not commonly used. Clinicians often use next-generation sequencing, which is less sensitive and can lead to false negatives.
It makes it difficult to know how to apply the findings to everyday practice, but Janne hopes a study will be done to correlate next-generation sequencing detection with outcomes.
The study was funded by AstraZeneca, maker of osimertinib, and researchers included AstraZeneca employees. Dr. Jänne is a consultant for and reported research funding from the company. He is a co-inventor on an EGFR mutations patent. Dr. Garassino is also an AstraZeneca consultant and reported institutional financial interests in the company.
A version of this article appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167833</fileName> <TBEID>0C04FC79.SIG</TBEID> <TBUniqueIdentifier>MD_0C04FC79</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240424T095456</QCDate> <firstPublished>20240424T095633</firstPublished> <LastPublished>20240424T095633</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240424T095633</CMSDate> <articleSource>FROM AACR</articleSource> <facebookInfo/> <meetingNumber>2976-24</meetingNumber> <byline>M Alex Otto</byline> <bylineText>M. ALEXANDER OTTO, PA, MMS</bylineText> <bylineFull>M. ALEXANDER OTTO, PA, MMS</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>When should patients with advanced or metastatic non–small cell lung cancer receive osimertinib plus platinum-based chemotherapy in the frontline setting and wh</metaDescription> <articlePDF/> <teaserImage/> <teaser>Randomized trial of 557 patients compares taking osimertinib alone to osimertinib with pemetrexed plus cisplatin or carboplatin, followed by pemetrexed.</teaser> <title>Is Osimertinib Better Alone or With Chemotherapy in Non–Small Cell Lung Cancer?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>chph</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term>6</term> <term canonical="true">31</term> </publications> <sections> <term>39313</term> <term>27980</term> <term canonical="true">53</term> </sections> <topics> <term>284</term> <term canonical="true">240</term> <term>270</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Is Osimertinib Better Alone or With Chemotherapy in Non–Small Cell Lung Cancer?</title> <deck/> </itemMeta> <itemContent> <p>SAN DIEGO — <span class="tag metaDescription">When should patients with advanced or metastatic non–small cell lung cancer receive osimertinib plus platinum-based chemotherapy in the frontline setting and when is osimertinib enough on its own?</span></p> <p>That is a question brewing among some oncologists now that the US Food and Drug Administration (FDA) <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/osimertinib-plus-chemo-approved-egfr-mutated-nsclc-2024a10003j5">has approved</a></span> osimertinib (Tagrisso, AstraZeneca) for both indications in patients with epidermal growth factor receptor (EGFR) mutations.<br/><br/>An answer began to emerge in research presented at the <span class="Hyperlink"><a href="https://www.medscape.com/viewcollection/37452">American Association for Cancer Research annual meeting</a></span>.<br/><br/>An <span class="Hyperlink"><a href="https://www.abstractsonline.com/pp8/#!/20272/presentation/11432">exploratory analysis</a> </span>of the <span class="Hyperlink"><a href="https://pubmed.ncbi.nlm.nih.gov/37937763/">FLAURA2</a></span> trial found that, when patients have EGFR mutations on baseline circulating tumor DNA (ctDNA) testing, the combination treatment can extend progression-free survival (PFS). In this patient group, those receiving osimertinib alongside <span class="Hyperlink">pemetrexed</span> plus <span class="Hyperlink">cisplatin</span> or <span class="Hyperlink">carboplatin</span> had a 9-month PFS advantage compared with those who received osimertinib alone.<br/><br/>Conversely, when patients do not have EGFR mutations following baseline ctDNA testing, osimertinib alone appears to offer similar PFS outcomes to the combination therapy, but with less toxicity.<br/><br/>“Baseline detection of plasma EGFR mutations may identify a subgroup of patients who derive most benefit from the addition of platinum-pemetrexed to osimertinib as first-line treatment of EGFR-mutated advance non–small cell lung cancer,” investigator <a href="https://www.dana-farber.org/find-a-doctor/pasi-a-janne"><span class="Hyperlink">Pasi A. J</span><span class="Hyperlink">ä</span><span class="Hyperlink">nne</span></a>, MD, PhD, a lung cancer oncologist at the Dana-Farber Cancer Institute, Boston, said during his presentation.<br/><br/>The FLAURA2 trial randomized 557 patients equally to daily osimertinib either alone or with pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by pemetrexed every 3 weeks until disease progression or unacceptable toxicity.<br/><br/>Patients were tested for Ex19del or L858R EGFR mutations at baseline and at 3 and 6 weeks; baseline mutations were found in 73% of evaluable patients.<br/><br/>In patients with baseline mutations, the median PFS was 24.8 months with the combination therapy vs 13.9 months with osimertinib alone (hazard ratio [HR], 0.60).<br/><br/>In patients without baseline mutations, the median PFS was similar in both groups — 33.3 months with the combination vs 30.3 months with monotherapy (HR, 0.93; 95% CI, 0.51-1.72).<br/><br/>The investigators also found that having baseline mutations was associated with worse outcomes regardless of study arm, and mutation clearance was associated with improved outcomes. Clearance occurred more quickly among patients receiving the combination treatment, but almost 90% of patients in both arms cleared their mutations by week 6.<br/><br/>“As we move forward and think about which of our patients we would treat with the combination ... the presence of baseline EGFR mutations in ctDNA may be one of the features that goes into the conversation,” Dr. J<span class="Hyperlink">ä</span>nne said.<br/><br/>Study discussant <span class="Hyperlink"><a href="https://www.uchicagomedicine.org/find-a-physician/physician/marina-chiara-garassino">Marina Chiara Garassino</a></span>, MD, a thoracic oncologist at the University of Chicago, agreed that this trial can help oncologists make this kind of treatment decision.<br/><br/>Patients with baseline EGFR mutations also tended to have larger tumors, more <span class="Hyperlink">brain metastases</span>, and worse performance scores; the combination therapy makes sense when such factors are present in patients with baseline EGFR mutations, Dr. Garassino said.<br/><br/>The wrinkle in the findings is that the study used digital droplet polymerase chain reaction (Biodesix) to test for EGFR mutations, which is not commonly used. Clinicians often use next-generation sequencing, which is less sensitive and can lead to false negatives.<br/><br/>It makes it difficult to know how to apply the findings to everyday practice, but Janne hopes a study will be done to correlate next-generation sequencing detection with outcomes.<br/><br/>The study was funded by AstraZeneca, maker of osimertinib, and researchers included AstraZeneca employees. Dr. J<span class="Hyperlink">ä</span>nne is a consultant for and reported research funding from the company. He is a co-inventor on an EGFR mutations patent. Dr. Garassino is also an AstraZeneca consultant and reported institutional financial interests in the company.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/osimertinib-better-alone-or-chemotherapy-nsclc-2024a10007sx">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM AACR
FDA Approves New Bladder Cancer Drug
Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease.
The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.
The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience.
Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2.
Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months.
According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.
The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.
The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.
The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity.
A version of this article appeared on Medscape.com.
Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease.
The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.
The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience.
Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2.
Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months.
According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.
The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.
The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.
The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity.
A version of this article appeared on Medscape.com.
Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease.
The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.
The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience.
Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2.
Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months.
According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.
The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.
The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.
The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity.
A version of this article appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167832</fileName> <TBEID>0C04FC77.SIG</TBEID> <TBUniqueIdentifier>MD_0C04FC77</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240424T091016</QCDate> <firstPublished>20240424T091038</firstPublished> <LastPublished>20240424T091038</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240424T091038</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>S Worcester</byline> <bylineText>SHARON WORCESTER, MA</bylineText> <bylineFull>SHARON WORCESTER, MA</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist nogapendekin alfa inbakicept-pmln (Anktiva), plus bac</metaDescription> <articlePDF/> <teaserImage/> <teaser>The FDA declined an initial approval for the combination in May 2023.</teaser> <title>FDA Approves New Bladder Cancer Drug</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> </publications> <sections> <term>39313</term> <term canonical="true">27979</term> <term>37225</term> <term>27980</term> </sections> <topics> <term>270</term> <term>278</term> <term canonical="true">214</term> <term>232</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>FDA Approves New Bladder Cancer Drug</title> <deck/> </itemMeta> <itemContent> <p> <span class="tag metaDescription">The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist <span class="Hyperlink"><a href="https://reference.medscape.com/drug/anktiva-nonapendekine-alfa-4000332">nogapendekin alfa</a></span> inbakicept-pmln (Anktiva), plus bacillus Calmette-Guérin (BCG), for the treatment of certain non–muscle-invasive bladder cancers that fail to respond to BCG alone.</span> </p> <p>Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive <span class="Hyperlink">bladder cancer</span> carcinoma in situ with or without Ta or T1 papillary disease. <br/><br/>The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which <span class="Hyperlink"><a href="https://immunitybio.com/fda-accepts-immunitybios-bla-resubmission-as-complete-and-sets-new-pdufa-date/">was accepted</a></span>.<br/><br/>The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a <span class="Hyperlink"><a href="https://immunitybio.com/nejm-evidence-publishes-results-for-immunitybios-quilt-3-032-registrational-trial-of-il-15-superagonist-n-803-plus-bcg-in-patients-with-bladder-cancer/">press release</a></span> announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience. <br/><br/>Approval was based on findings from the single arm, phase 2/3 open-label <span class="Hyperlink"><a href="https://classic.clinicaltrials.gov/ct2/show/NCT03022825">QUILT-3.032 study</a></span>, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2. <br/><br/>Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. <br/><br/>According to the <span class="Hyperlink"><a href="https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer">FDA’s press release</a></span>, 62% of patients had a complete response, defined as a negative <span class="Hyperlink">cystoscopy</span> and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.<br/><br/>The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and <span class="Hyperlink">hematuria</span>, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.<br/><br/>The <span class="Hyperlink"><a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761336s000lbl.pdf">recommended dose</a></span> is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.<br/><br/>The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity. <br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/fda-approves-new-bladder-cancer-drug-2024a10007t5">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
How Can Kidney Cancer Patients Benefit From New Combination Therapy?
Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.
A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.
Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
Tips for Evaluating Risk When Treating Renal Cell Carcinoma?
For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.
For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?
The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.
Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.
Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.
The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.
Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
Where Do VEGF-TKIs Fit In?
VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.
In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.
The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).
Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.
Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.
However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?
Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.
Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.
For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?
“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.
However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.
Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.
Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.
Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.
Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.
A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.
Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
Tips for Evaluating Risk When Treating Renal Cell Carcinoma?
For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.
For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?
The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.
Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.
Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.
The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.
Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
Where Do VEGF-TKIs Fit In?
VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.
In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.
The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).
Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.
Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.
However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?
Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.
Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.
For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?
“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.
However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.
Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.
Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.
Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.
Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.
A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.
Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
Tips for Evaluating Risk When Treating Renal Cell Carcinoma?
For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.
For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?
The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.
Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.
Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.
The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.
Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
Where Do VEGF-TKIs Fit In?
VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.
In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.
The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).
Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.
Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.
However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?
Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.
Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.
For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?
“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.
However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.
Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.
Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.
Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimiz</metaDescription> <articlePDF/> <teaserImage/> <teaser>Immunotherapy has expanded treatment options as an adjuvant and a first-line therapy in patients with renal cell carcinoma. </teaser> <title>How Can Kidney Cancer Patients Benefit From New Combination Therapy?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>GIHOLD</publicationCode> <pubIssueName>January 2014</pubIssueName> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> </publications> <sections> <term>27980</term> <term>39313</term> <term canonical="true">53</term> </sections> <topics> <term>67020</term> <term>270</term> <term canonical="true">31848</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>How Can Kidney Cancer Patients Benefit From New Combination Therapy?</title> <deck/> </itemMeta> <itemContent> <p> <span class="tag metaDescription">The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimize outcomes, according to a medical oncologist from the Dana-Farber Cancer Institute, Boston.</span> </p> <p>Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.<br/><br/>A systematic <a href="https://www.sciencedirect.com/science/article/pii/S2666168321034066?via%3Dihub">review and meta-analysis</a> published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma. <br/><br/>Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.<br/><br/></p> <h2>Tips for Evaluating Risk When Treating Renal Cell Carcinoma? </h2> <p>For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy. </p> <p>For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.<br/><br/></p> <h2>What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma? </h2> <p>The US Food and Drug Administration (FDA) <a href="https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-renal-cell-carcinoma">approved pembrolizumab</a> in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions. </p> <p>Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the <a href="https://ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.LBA359">KEYNOTE-564 study, published in 2024</a> in the <em>Journal of Clinical Oncology</em>, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo. <br/><br/>Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted. <br/><br/>The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (<span class="Hyperlink"><a href="https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1440">Version: 3.2024</a></span>), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said. <br/><br/>Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.<br/><br/></p> <h2>Where Do VEGF-TKIs Fit In? </h2> <p>VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the <em>Journal of Clinical Oncology</em> in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups. </p> <p>In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted. <br/><br/>The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months). <br/><br/>Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.<br/><br/>Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events. <br/><br/>However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said. <br/><br/></p> <h2>What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now? </h2> <p>Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent <a href="https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1133832/full">review</a> published in <em>Frontiers in Oncology</em>. </p> <p>Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (V<span class="Hyperlink">ersion: 3.2024</span>) that had been updated in 2024.<br/><br/>For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab. <br/><br/>For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab. <br/><br/>For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib. <br/><br/></p> <h2>What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?</h2> <p>“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.</p> <p>However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said. <br/><br/>Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said. <br/><br/>Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said. <br/><br/>Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM NCCN 2024
New Federal Rule Delivers Workplace Support, Time Off for Pregnant Docs
Pregnant physicians may receive more workplace accommodations and protection against discrimination thanks to an updated rule from the US Equal Employment Opportunity Commission (EEOC). The guidelines could prevent women from losing critical career momentum.
The Pregnant Workers Fairness Act (PWFA) aims to help workers balance professional demands with healthy pregnancies. It requires employers to provide reasonable accommodations for a “worker’s known limitations,” including physical or mental conditions associated with “pregnancy, childbirth, or related medical conditions.”
Reasonable accommodations vary but may involve time off to attend healthcare appointments or recover from childbirth, extra breaks during a shift, shorter work hours, or the ability to sit instead of stand. Private and public sector employers, including state and local governments, federal agencies, and employment agencies, must abide by the new guidelines unless they can provide evidence that doing so will cause undue hardship.
Female doctors have historically encountered significant barriers to family planning. Years of training cause them to delay having children, often leading to higher rates of infertility, miscarriage, and pregnancy complications than in the general population.
Some specialties, like surgeons, are particularly at risk, with 42% reporting at least one pregnancy loss. Most surgeons work their regular schedules until delivery despite desiring workload reductions, commonly citing unsupportive workplaces as a reason for not seeking accommodations.
Trauma surgeon Qaali Hussein, MD, became pregnant with her first child during her intern year in 2008. She told this news organization that her residency program didn’t even have a maternity policy at the time, and her male supervisor was certain that motherhood would end her surgical career.
She shared how “women usually waited until the end of their training to get pregnant. No one had ever gotten pregnant during the program and returned from maternity leave. I was the first to do so, so there wasn’t a policy or any program support to say, ‘What can we do to help?’ ”
Dr. Hussein used her vacation and sick time, returning to work 4 weeks after delivery. She had five more children, including twins her chief year and another baby during fellowship training in 2014.
Each subsequent pregnancy was met with the same response from program leadership, she recalled. “They’d say, ‘This is it. You may have been able to do the first and second child, but this one will be impossible.’ ”
After the PWFA regulations first became enforceable in June, the EEOC accepted public feedback. The guidelines received nearly 100,000 comments, spurred mainly by the inclusion of abortion care as a qualifying condition for which an employee could receive accommodations. About 54,000 comments called for abortion to be excluded from the final rule, and 40,000 supported keeping the clause.
The EEOC issued the final rule on April 15. It includes abortion care. However, the updated rule “does not require any employee to have — or not to have — an abortion, does not require taxpayers to pay for any abortions, and does not compel health care providers to provide any abortions,” the unpublished version of the final rule said. It is scheduled to take effect 60 days after its publication in the Federal Register on April 19.
Increasing Support for Doctor-Moms
The PWFA supplements other EEOC protections, such as pregnancy discrimination under Title VII of the Civil Rights Act of 1964 and access to reasonable accommodations under the Americans with Disabilities Act. In addition, it builds upon Department of Labor regulations, like the PUMP Act for breastfeeding employees and the Family and Medical Leave Act, which provides 12 weeks of unpaid, job-protected leave for the arrival of a child or certain medical conditions.
FMLA applies only to employees who have worked full-time for at least 12 months for an employer with 50 or more employees. Meanwhile, the unpaid, job-protected leave under the PWFA has no waiting period, lowers the required number of employees to 15, and permits accommodations for up to 40 weeks.
Employers are encouraged to honor “common and simple” requests, like using a closer parking space or pumping or nursing at work, without requiring a doctor’s note, the rule said.
Efforts to improve family leave policies for physicians and residents have been gaining traction. In 2021, the American Board of Medical Specialties began requiring its member boards with training programs lasting 2 or more years to allow at least 6 weeks off for parental, caregiver, and medical leave. This time can be taken without exhausting vacation or sick leave or requiring an extension in training. Over half of the 24 member boards permit leave beyond 6 weeks, including the American Boards of Allergy and Immunology, Emergency Medicine, Family Medicine, Radiology, and Surgery.
Estefania Oliveros, MD, MSc, cardiologist and assistant professor at the Lewis Katz School of Medicine at Temple University, Philadelphia, told this news organization that the Accreditation Council for Graduate Medical Education also requires that residents and fellows receive 6 weeks of paid leave.
“We add to that vacation time, so it gives them at least 8 weeks,” she said. The school has created spaces for nursing mothers — something neither she nor Dr. Hussein had access to when breastfeeding — and encourages the attendings to be proactive in excusing pregnant fellows for appointments.
This differs significantly from her fellowship training experience 6 years ago at another institution, where she worked without accommodations until the day before her cesarean delivery. Dr. Oliveros had to use all her vacation time for recovery, returning to the program after 4 weeks instead of the recommended 6.
“And that’s the story you hear all the time. Not because people are ill-intended; I just don’t think the system is designed to accommodate women, so we lose a lot of talent that way,” said Dr. Oliveros, whose 2019 survey in the Journal of the American College of Cardiology called for more support and protections for pregnant doctors.
Both doctors believe the PWFA will be beneficial but only if leadership in the field takes up the cause.
“The cultures of these institutions determine whether women feel safe or even confident enough to have children in medical school or residency,” said Dr. Hussein.
A version of this article appeared on Medscape.com.
Pregnant physicians may receive more workplace accommodations and protection against discrimination thanks to an updated rule from the US Equal Employment Opportunity Commission (EEOC). The guidelines could prevent women from losing critical career momentum.
The Pregnant Workers Fairness Act (PWFA) aims to help workers balance professional demands with healthy pregnancies. It requires employers to provide reasonable accommodations for a “worker’s known limitations,” including physical or mental conditions associated with “pregnancy, childbirth, or related medical conditions.”
Reasonable accommodations vary but may involve time off to attend healthcare appointments or recover from childbirth, extra breaks during a shift, shorter work hours, or the ability to sit instead of stand. Private and public sector employers, including state and local governments, federal agencies, and employment agencies, must abide by the new guidelines unless they can provide evidence that doing so will cause undue hardship.
Female doctors have historically encountered significant barriers to family planning. Years of training cause them to delay having children, often leading to higher rates of infertility, miscarriage, and pregnancy complications than in the general population.
Some specialties, like surgeons, are particularly at risk, with 42% reporting at least one pregnancy loss. Most surgeons work their regular schedules until delivery despite desiring workload reductions, commonly citing unsupportive workplaces as a reason for not seeking accommodations.
Trauma surgeon Qaali Hussein, MD, became pregnant with her first child during her intern year in 2008. She told this news organization that her residency program didn’t even have a maternity policy at the time, and her male supervisor was certain that motherhood would end her surgical career.
She shared how “women usually waited until the end of their training to get pregnant. No one had ever gotten pregnant during the program and returned from maternity leave. I was the first to do so, so there wasn’t a policy or any program support to say, ‘What can we do to help?’ ”
Dr. Hussein used her vacation and sick time, returning to work 4 weeks after delivery. She had five more children, including twins her chief year and another baby during fellowship training in 2014.
Each subsequent pregnancy was met with the same response from program leadership, she recalled. “They’d say, ‘This is it. You may have been able to do the first and second child, but this one will be impossible.’ ”
After the PWFA regulations first became enforceable in June, the EEOC accepted public feedback. The guidelines received nearly 100,000 comments, spurred mainly by the inclusion of abortion care as a qualifying condition for which an employee could receive accommodations. About 54,000 comments called for abortion to be excluded from the final rule, and 40,000 supported keeping the clause.
The EEOC issued the final rule on April 15. It includes abortion care. However, the updated rule “does not require any employee to have — or not to have — an abortion, does not require taxpayers to pay for any abortions, and does not compel health care providers to provide any abortions,” the unpublished version of the final rule said. It is scheduled to take effect 60 days after its publication in the Federal Register on April 19.
Increasing Support for Doctor-Moms
The PWFA supplements other EEOC protections, such as pregnancy discrimination under Title VII of the Civil Rights Act of 1964 and access to reasonable accommodations under the Americans with Disabilities Act. In addition, it builds upon Department of Labor regulations, like the PUMP Act for breastfeeding employees and the Family and Medical Leave Act, which provides 12 weeks of unpaid, job-protected leave for the arrival of a child or certain medical conditions.
FMLA applies only to employees who have worked full-time for at least 12 months for an employer with 50 or more employees. Meanwhile, the unpaid, job-protected leave under the PWFA has no waiting period, lowers the required number of employees to 15, and permits accommodations for up to 40 weeks.
Employers are encouraged to honor “common and simple” requests, like using a closer parking space or pumping or nursing at work, without requiring a doctor’s note, the rule said.
Efforts to improve family leave policies for physicians and residents have been gaining traction. In 2021, the American Board of Medical Specialties began requiring its member boards with training programs lasting 2 or more years to allow at least 6 weeks off for parental, caregiver, and medical leave. This time can be taken without exhausting vacation or sick leave or requiring an extension in training. Over half of the 24 member boards permit leave beyond 6 weeks, including the American Boards of Allergy and Immunology, Emergency Medicine, Family Medicine, Radiology, and Surgery.
Estefania Oliveros, MD, MSc, cardiologist and assistant professor at the Lewis Katz School of Medicine at Temple University, Philadelphia, told this news organization that the Accreditation Council for Graduate Medical Education also requires that residents and fellows receive 6 weeks of paid leave.
“We add to that vacation time, so it gives them at least 8 weeks,” she said. The school has created spaces for nursing mothers — something neither she nor Dr. Hussein had access to when breastfeeding — and encourages the attendings to be proactive in excusing pregnant fellows for appointments.
This differs significantly from her fellowship training experience 6 years ago at another institution, where she worked without accommodations until the day before her cesarean delivery. Dr. Oliveros had to use all her vacation time for recovery, returning to the program after 4 weeks instead of the recommended 6.
“And that’s the story you hear all the time. Not because people are ill-intended; I just don’t think the system is designed to accommodate women, so we lose a lot of talent that way,” said Dr. Oliveros, whose 2019 survey in the Journal of the American College of Cardiology called for more support and protections for pregnant doctors.
Both doctors believe the PWFA will be beneficial but only if leadership in the field takes up the cause.
“The cultures of these institutions determine whether women feel safe or even confident enough to have children in medical school or residency,” said Dr. Hussein.
A version of this article appeared on Medscape.com.
Pregnant physicians may receive more workplace accommodations and protection against discrimination thanks to an updated rule from the US Equal Employment Opportunity Commission (EEOC). The guidelines could prevent women from losing critical career momentum.
The Pregnant Workers Fairness Act (PWFA) aims to help workers balance professional demands with healthy pregnancies. It requires employers to provide reasonable accommodations for a “worker’s known limitations,” including physical or mental conditions associated with “pregnancy, childbirth, or related medical conditions.”
Reasonable accommodations vary but may involve time off to attend healthcare appointments or recover from childbirth, extra breaks during a shift, shorter work hours, or the ability to sit instead of stand. Private and public sector employers, including state and local governments, federal agencies, and employment agencies, must abide by the new guidelines unless they can provide evidence that doing so will cause undue hardship.
Female doctors have historically encountered significant barriers to family planning. Years of training cause them to delay having children, often leading to higher rates of infertility, miscarriage, and pregnancy complications than in the general population.
Some specialties, like surgeons, are particularly at risk, with 42% reporting at least one pregnancy loss. Most surgeons work their regular schedules until delivery despite desiring workload reductions, commonly citing unsupportive workplaces as a reason for not seeking accommodations.
Trauma surgeon Qaali Hussein, MD, became pregnant with her first child during her intern year in 2008. She told this news organization that her residency program didn’t even have a maternity policy at the time, and her male supervisor was certain that motherhood would end her surgical career.
She shared how “women usually waited until the end of their training to get pregnant. No one had ever gotten pregnant during the program and returned from maternity leave. I was the first to do so, so there wasn’t a policy or any program support to say, ‘What can we do to help?’ ”
Dr. Hussein used her vacation and sick time, returning to work 4 weeks after delivery. She had five more children, including twins her chief year and another baby during fellowship training in 2014.
Each subsequent pregnancy was met with the same response from program leadership, she recalled. “They’d say, ‘This is it. You may have been able to do the first and second child, but this one will be impossible.’ ”
After the PWFA regulations first became enforceable in June, the EEOC accepted public feedback. The guidelines received nearly 100,000 comments, spurred mainly by the inclusion of abortion care as a qualifying condition for which an employee could receive accommodations. About 54,000 comments called for abortion to be excluded from the final rule, and 40,000 supported keeping the clause.
The EEOC issued the final rule on April 15. It includes abortion care. However, the updated rule “does not require any employee to have — or not to have — an abortion, does not require taxpayers to pay for any abortions, and does not compel health care providers to provide any abortions,” the unpublished version of the final rule said. It is scheduled to take effect 60 days after its publication in the Federal Register on April 19.
Increasing Support for Doctor-Moms
The PWFA supplements other EEOC protections, such as pregnancy discrimination under Title VII of the Civil Rights Act of 1964 and access to reasonable accommodations under the Americans with Disabilities Act. In addition, it builds upon Department of Labor regulations, like the PUMP Act for breastfeeding employees and the Family and Medical Leave Act, which provides 12 weeks of unpaid, job-protected leave for the arrival of a child or certain medical conditions.
FMLA applies only to employees who have worked full-time for at least 12 months for an employer with 50 or more employees. Meanwhile, the unpaid, job-protected leave under the PWFA has no waiting period, lowers the required number of employees to 15, and permits accommodations for up to 40 weeks.
Employers are encouraged to honor “common and simple” requests, like using a closer parking space or pumping or nursing at work, without requiring a doctor’s note, the rule said.
Efforts to improve family leave policies for physicians and residents have been gaining traction. In 2021, the American Board of Medical Specialties began requiring its member boards with training programs lasting 2 or more years to allow at least 6 weeks off for parental, caregiver, and medical leave. This time can be taken without exhausting vacation or sick leave or requiring an extension in training. Over half of the 24 member boards permit leave beyond 6 weeks, including the American Boards of Allergy and Immunology, Emergency Medicine, Family Medicine, Radiology, and Surgery.
Estefania Oliveros, MD, MSc, cardiologist and assistant professor at the Lewis Katz School of Medicine at Temple University, Philadelphia, told this news organization that the Accreditation Council for Graduate Medical Education also requires that residents and fellows receive 6 weeks of paid leave.
“We add to that vacation time, so it gives them at least 8 weeks,” she said. The school has created spaces for nursing mothers — something neither she nor Dr. Hussein had access to when breastfeeding — and encourages the attendings to be proactive in excusing pregnant fellows for appointments.
This differs significantly from her fellowship training experience 6 years ago at another institution, where she worked without accommodations until the day before her cesarean delivery. Dr. Oliveros had to use all her vacation time for recovery, returning to the program after 4 weeks instead of the recommended 6.
“And that’s the story you hear all the time. Not because people are ill-intended; I just don’t think the system is designed to accommodate women, so we lose a lot of talent that way,” said Dr. Oliveros, whose 2019 survey in the Journal of the American College of Cardiology called for more support and protections for pregnant doctors.
Both doctors believe the PWFA will be beneficial but only if leadership in the field takes up the cause.
“The cultures of these institutions determine whether women feel safe or even confident enough to have children in medical school or residency,” said Dr. Hussein.
A version of this article appeared on Medscape.com.
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<pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> </publications_g> <publications> <term canonical="true">21</term> <term>26</term> <term>25</term> <term>31</term> <term>23</term> <term>22</term> <term>52226</term> <term>58877</term> <term>51892</term> <term>18</term> <term>15</term> <term>13</term> <term>9</term> <term>34</term> <term>6</term> <term>5</term> </publications> <sections> <term canonical="true">27980</term> <term>39313</term> </sections> <topics> <term>322</term> <term canonical="true">38029</term> <term>50194</term> <term>278</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>New Federal Rule Delivers Workplace Support, Time Off for Pregnant Docs</title> <deck/> </itemMeta> <itemContent> <p>Pregnant physicians may receive more workplace accommodations and protection against discrimination thanks to an updated rule from the US Equal Employment Opportunity Commission (EEOC). The guidelines could prevent women from losing critical career momentum. </p> <p>The <span class="Hyperlink"><a href="https://www.eeoc.gov/newsroom/eeoc-issues-final-regulation-pregnant-workers-fairness-act">Pregnant Workers Fairness Act (PWFA)</a></span> aims to help workers balance professional demands with healthy pregnancies. It requires employers to provide reasonable accommodations for a “worker’s known limitations,” including physical or <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/restricted-abortion-access-tied-mental-health-harm-2024a10001u9">mental conditions</a></span> associated with “pregnancy, childbirth, or related medical conditions.”<br/><br/>Reasonable accommodations vary but may involve time off to attend healthcare appointments or recover from childbirth, extra breaks during a shift, shorter work hours, or the ability to sit instead of stand. Private and public sector employers, including state and local governments, federal agencies, and employment agencies, must abide by the new guidelines unless they can provide evidence that doing so will cause undue hardship. <br/><br/>Female doctors have historically encountered <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/987608">significant barriers</a></span> to family planning. Years of training cause them to delay having children, often leading to higher rates of <span class="Hyperlink">infertility</span>, <span class="Hyperlink">miscarriage</span>, and pregnancy complications than in the general population. <br/><br/>Some specialties, like surgeons, are particularly <span class="Hyperlink"><a href="https://www.sciencedirect.com/science/article/abs/pii/S0022480423000987">at risk</a></span>, with 42% reporting at least one <span class="Hyperlink"><a href="https://reference.medscape.com/article/266317-overview">pregnancy loss</a></span>. Most surgeons work their regular schedules until delivery despite desiring workload reductions, commonly citing unsupportive workplaces as a reason for not seeking accommodations. <br/><br/>Trauma surgeon Qaali Hussein, MD, became pregnant with her first child during her intern year in 2008. She told this news organization that her residency program didn’t even have a maternity policy at the time, and her male supervisor was certain that motherhood would end her surgical career. <br/><br/>She shared how “women usually waited until the end of their training to get pregnant. No one had ever gotten pregnant during the program and returned from maternity leave. I was the first to do so, so there wasn’t a policy or any program support to say, ‘What can we do to help?’ ”<br/><br/>Dr. Hussein used her vacation and sick time, returning to work 4 weeks after delivery. She had five more children, including twins her chief year and another baby during fellowship training in 2014. <br/><br/>Each subsequent pregnancy was met with the same response from program leadership, she recalled. “They’d say, ‘This is it. You may have been able to do the first and second child, but this one will be impossible.’ ”<br/><br/>After the PWFA regulations first became enforceable in June, the EEOC accepted public feedback. The guidelines received <span class="Hyperlink"><a href="https://www.regulations.gov/document/EEOC-2023-0004-0001">nearly 100,000 comments</a></span>, spurred mainly by the inclusion of abortion care as a qualifying condition for which an employee could receive accommodations. About 54,000 comments called for abortion to be excluded from the final rule, and 40,000 supported keeping the clause. <br/><br/>The EEOC issued the final rule on April 15. It includes abortion care. However, the updated rule “does not require any employee to have — or not to have — an abortion, does not require taxpayers to pay for any abortions, and does not compel health care providers to provide any abortions,” the <span class="Hyperlink"><a href="https://www.federalregister.gov/public-inspection/2024-07527/implementation-of-the-pregnant-workers-fairness-act">unpublished version</a></span> of the final rule said. It is scheduled to take effect 60 days after its publication in the Federal Register on April 19.<br/><br/></p> <h2>Increasing Support for Doctor-Moms</h2> <p>The PWFA supplements other EEOC protections, such as pregnancy discrimination under Title VII of the Civil Rights Act of 1964 and access to reasonable accommodations under the Americans with Disabilities Act. In addition, it builds upon Department of Labor regulations, like the PUMP Act for <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/979276">breastfeeding employees</a></span> and the Family and Medical Leave Act, which provides 12 weeks of unpaid, job-protected leave for the arrival of a child or certain medical conditions.</p> <p>FMLA applies only to employees who have worked full-time for at least 12 months for an employer with 50 or more employees. Meanwhile, the unpaid, job-protected leave under the PWFA has no waiting period, lowers the required number of employees to 15, and permits accommodations for up to 40 weeks. <br/><br/>Employers are encouraged to honor “common and simple” requests, like using a closer parking space or pumping or nursing at work, without requiring a doctor’s note, the rule said. <br/><br/>Efforts to improve family leave policies for physicians and residents have been gaining traction. In 2021, the American Board of Medical Specialties began <span class="Hyperlink"><a href="https://www.abms.org/newsroom/abms-member-boards-leave-policies-help-residents-care-for-their-own-families/">requiring its member boards</a></span> with training programs lasting 2 or more years to allow at least 6 weeks off for parental, caregiver, and medical leave. This time can be taken without exhausting vacation or sick leave or requiring an extension in training. Over half of the 24 member boards permit leave beyond 6 weeks, including the American Boards of Allergy and Immunology, Emergency Medicine, Family Medicine, Radiology, and Surgery. <br/><br/>Estefania Oliveros, MD, MSc, cardiologist and assistant professor at the Lewis Katz School of Medicine at Temple University, Philadelphia, told this news organization that the Accreditation Council for Graduate Medical Education also requires that residents and fellows receive <span class="Hyperlink">6 weeks of paid leave</span>. <br/><br/>“We add to that vacation time, so it gives them at least 8 weeks,” she said. The school has created spaces for nursing mothers — something neither she nor Dr. Hussein had access to when breastfeeding — and encourages the attendings to be proactive in excusing pregnant fellows for appointments. <br/><br/>This differs significantly from her fellowship training experience 6 years ago at another institution, where she worked without accommodations until the day before her <span class="Hyperlink">cesarean delivery</span>. Dr. Oliveros had to use all her vacation time for recovery, returning to the program after 4 weeks instead of the recommended 6. <br/><br/>“And that’s the story you hear all the time. Not because people are ill-intended; I just don’t think the system is designed to accommodate women, so we lose a lot of talent that way,” said Dr. Oliveros, whose 2019 <span class="Hyperlink"><a href="https://www.jacc.org/doi/10.1016/j.jaccas.2019.05.028">survey</a></span> in the <em>Journal of the American College of Cardiology</em> called for more support and protections for pregnant doctors. <br/><br/>Both doctors believe the PWFA will be beneficial but only if leadership in the field takes up the cause. <br/><br/>“The cultures of these institutions determine whether women feel safe or even confident enough to have children in medical school or residency,” said Dr. Hussein. <br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/new-federal-rule-delivers-workplace-support-time-pregnant-2024a10007k1">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Both Promise and Concern for OSA and CPAP with GLP-1s
Will the weight reduction success with glucagon-like peptide-1 (GLP-1) agonists translate into strong reductions in obstructive sleep apnea (OSA)? Will those potential OSA benefits obviate the need in many for continuous positive airway pressure (CPAP)?
“I think it’s a game changer for helping people who are overweight or obese,” Samuel T. Kuna, MD, chief of sleep medicine at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, said in an interview with CHEST Physician. “I think we’re just starting out on a very exciting new era. We finally have quite effective treatments for this population.” Dr. Kuna’s Sleep AHEAD (Action for Health in Diabetes) 2021 study (doi: 10.1164/rccm.201912-2511OC) found that participants with OSA and type 2 diabetes mellitus receiving intensive lifestyle interventions for weight loss had reduced OSA severity at 10 years, and that OSA remission at 10 years was more common with intensive lifestyle intervention than with diabetes support and education.
Potential for OSA impact
In a JAMA Network Open/Pulmonary Medicine article on a 2022 study (doi: 10.1001/jamanetworkopen.2022.8212) conducted among 89 Spanish male adults with moderate to severe OSA and body mass index of 25 or greater, participants received CPAP therapy with or without 8 weeks of weight loss and lifestyle intervention. The primary endpoint of apnea-hypopnea index at 6 months showed the intervention to yield “clinically meaningful and sustainable improvements in OSA.”
Dr. Kuna stated, “I don’t think these [weight loss] agents eliminate the importance of behavioral modification, of changing diet, of reducing highly processed foods and maintaining a healthy lifestyle.” He acknowledged, however, that behavioral endeavors have been in general disappointing with respect to patients’ ability to achieve weight loss. “These medicines really open up a new strategy to help patients do that,” he added.
Dr. Kuna pointed to a recent (2023) Grunstein et al. perspective article (doi: 10.1093/sleep/zsad224) published in Sleep citing phase 3 trial results showing placebo-subtracted weight loss percentages. With subcutaneous (SC) semaglutide 2.4 mg they were 12.6% in patients with obesity or overweight with one or more weight-related comorbidities (but not type 2 diabetes), and 17.8% with tirzepatide (15 mg, SC, weekly), a combination GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, in a similar population. The authors stated, “These new agents, provided they are available to persons who need them most — who are often socioeconomically disadvantaged — could revolutionize the management of obesity and its many complications, including OSA.” Grunstein et al. also, noted that the number of studies showing improvement in cardiometabolic outcomes (eg, blood pressure) with pre-incretin OSA therapies are “minimal.” They underscored, however, the need for risk/benefit/cost-effectiveness data on incretin therapies, and cited evidence that withdrawal from incretin treatment brings back weight gain and adverse cardiometabolic factors. They also indicated key areas of uncertainty requiring research: gender-based response differences to incretins (women predominate in most weight loss studies, but OSA is more common in men), how CPAP users will adapt to incretin OSA benefits, direct comparisons of impact on OSA with incretins vs mechanical therapy, and understanding which target populations derive the most benefit with incretin therapies.
Despite the unanswered questions, the direction was unequivocally clear for Grunstein et al.: “Ultimately, the focus must shift away from mechanical therapy for obesity-related OSA towards weight loss, the latter which is likely to produce multiple health outcome improvements that are superior, including all-cause mortality.”
Dr. Kuna agreed with the Sleep article authors that one implication of this “incretin revolution” is that sleep physicians will have to broaden their skills to encompass obesity management. “As the field evolves, perhaps we should start training our fellows about how to manage these patients,” Dr. Kuna said.
Significant impact on OSA and CPAP
“Obesity is a risk factor for sleep apnea,” stated Saadia A. Faiz, MD, FCCP, professor, Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, “so with increased use of these GLP-1 agents for weight reduction, we would anticipate a significant impact on both OSA severity and need for CPAP.” Speaking in a CHEST Physician interview and referring to the Kuna et al. study, she stated, “Since cessation of the drug can lead to rebound weight gain, the emphasis on healthy eating and exercise is crucial to management.” Dr. Faiz said further, “It’s important to note that there are other weight-independent mechanisms for OSA, including upper airway anatomy, mechanisms that modulate upper airway stability, chemoreceptor sensitivity, visceral adiposity, neuroendocrine control, sleep quality, and other aspects of OSA pathophysiology yet to be discovered.”
Cost an obstacle for some
“For many insurances, criteria for coverage include obesity and prediabetes based on HbA1c. For some not meeting requirements, they will have to pay out of pocket,” Dr. Faiz said. She pointed to a Respirology (doi: 10.1111/resp.14545) commentary in which Garun S. Hamilton, MBBS, PhD, and Bradley A. Edwards, PhD, underscored the nearly 1 billion people worldwide with OSA, most of whom are overweight or obese. “GLP-1 agonists are so effective that they have become a worldwide phenomenon. The high cost of the medications combined with the high prevalence of OSA means that there is no way that universal healthcare funding schemes can afford these medications, unless strict criteria are in place to prioritize those who can gain subsidized access and/or a duration of use limit is in place,” they stated. “This will no doubt exacerbate inequities in healthcare access and outcome between those from lower versus higher socioeconomic populations, as the attributable benefit from GLP-1 agonists is likely to be dependent on a patient’s ability to afford them.”
Beyond health equity concerns
The evidence for clinically relevant reductions in weight and resultant lowering of other adverse risk factors supports a wide embrace of Ozempic-type drugs. Standing alongside, however, are the cautionary pleas of nutrition/lifestyle-focused health advocates. They urge that prescriptions for nonpharmacological strategies that promote better sleep, healthier food choices, and more exercise need sharper highlighting and strong incentivizing.
Dr. Faiz said, “The availability and consumption of ultra-processed foods can impact food intake and weight. Specifically, in a small study of 20 inpatient adults admitted to the NIH Clinical Center randomized to either ultra-processed or unprocessed diets for 14 days, increased caloric intake and weight gain were found in the ultra-processed cohort.” In the study Dr. Faiz cited (doi: 10.1016/j.cmet.2019.05.008), meals were matched for calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Analysis showed a 4-pound weight difference between groups within 2 weeks: The ultra-processed cohort had taken in an extra 500 calories a day and had gained weight (0.9 ± 0.3 kg [P = .009]) and body fat while the unprocessed food group lost weight (0.9 ± 0.3 kg [P = .007]) and body fat.
“Thus, the type of foods we opt for can also have significant impact,” Dr. Faiz stated.
Dr. Faiz and Dr. Kuna said they had no conflicts of interest to disclose.
Will the weight reduction success with glucagon-like peptide-1 (GLP-1) agonists translate into strong reductions in obstructive sleep apnea (OSA)? Will those potential OSA benefits obviate the need in many for continuous positive airway pressure (CPAP)?
“I think it’s a game changer for helping people who are overweight or obese,” Samuel T. Kuna, MD, chief of sleep medicine at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, said in an interview with CHEST Physician. “I think we’re just starting out on a very exciting new era. We finally have quite effective treatments for this population.” Dr. Kuna’s Sleep AHEAD (Action for Health in Diabetes) 2021 study (doi: 10.1164/rccm.201912-2511OC) found that participants with OSA and type 2 diabetes mellitus receiving intensive lifestyle interventions for weight loss had reduced OSA severity at 10 years, and that OSA remission at 10 years was more common with intensive lifestyle intervention than with diabetes support and education.
Potential for OSA impact
In a JAMA Network Open/Pulmonary Medicine article on a 2022 study (doi: 10.1001/jamanetworkopen.2022.8212) conducted among 89 Spanish male adults with moderate to severe OSA and body mass index of 25 or greater, participants received CPAP therapy with or without 8 weeks of weight loss and lifestyle intervention. The primary endpoint of apnea-hypopnea index at 6 months showed the intervention to yield “clinically meaningful and sustainable improvements in OSA.”
Dr. Kuna stated, “I don’t think these [weight loss] agents eliminate the importance of behavioral modification, of changing diet, of reducing highly processed foods and maintaining a healthy lifestyle.” He acknowledged, however, that behavioral endeavors have been in general disappointing with respect to patients’ ability to achieve weight loss. “These medicines really open up a new strategy to help patients do that,” he added.
Dr. Kuna pointed to a recent (2023) Grunstein et al. perspective article (doi: 10.1093/sleep/zsad224) published in Sleep citing phase 3 trial results showing placebo-subtracted weight loss percentages. With subcutaneous (SC) semaglutide 2.4 mg they were 12.6% in patients with obesity or overweight with one or more weight-related comorbidities (but not type 2 diabetes), and 17.8% with tirzepatide (15 mg, SC, weekly), a combination GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, in a similar population. The authors stated, “These new agents, provided they are available to persons who need them most — who are often socioeconomically disadvantaged — could revolutionize the management of obesity and its many complications, including OSA.” Grunstein et al. also, noted that the number of studies showing improvement in cardiometabolic outcomes (eg, blood pressure) with pre-incretin OSA therapies are “minimal.” They underscored, however, the need for risk/benefit/cost-effectiveness data on incretin therapies, and cited evidence that withdrawal from incretin treatment brings back weight gain and adverse cardiometabolic factors. They also indicated key areas of uncertainty requiring research: gender-based response differences to incretins (women predominate in most weight loss studies, but OSA is more common in men), how CPAP users will adapt to incretin OSA benefits, direct comparisons of impact on OSA with incretins vs mechanical therapy, and understanding which target populations derive the most benefit with incretin therapies.
Despite the unanswered questions, the direction was unequivocally clear for Grunstein et al.: “Ultimately, the focus must shift away from mechanical therapy for obesity-related OSA towards weight loss, the latter which is likely to produce multiple health outcome improvements that are superior, including all-cause mortality.”
Dr. Kuna agreed with the Sleep article authors that one implication of this “incretin revolution” is that sleep physicians will have to broaden their skills to encompass obesity management. “As the field evolves, perhaps we should start training our fellows about how to manage these patients,” Dr. Kuna said.
Significant impact on OSA and CPAP
“Obesity is a risk factor for sleep apnea,” stated Saadia A. Faiz, MD, FCCP, professor, Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, “so with increased use of these GLP-1 agents for weight reduction, we would anticipate a significant impact on both OSA severity and need for CPAP.” Speaking in a CHEST Physician interview and referring to the Kuna et al. study, she stated, “Since cessation of the drug can lead to rebound weight gain, the emphasis on healthy eating and exercise is crucial to management.” Dr. Faiz said further, “It’s important to note that there are other weight-independent mechanisms for OSA, including upper airway anatomy, mechanisms that modulate upper airway stability, chemoreceptor sensitivity, visceral adiposity, neuroendocrine control, sleep quality, and other aspects of OSA pathophysiology yet to be discovered.”
Cost an obstacle for some
“For many insurances, criteria for coverage include obesity and prediabetes based on HbA1c. For some not meeting requirements, they will have to pay out of pocket,” Dr. Faiz said. She pointed to a Respirology (doi: 10.1111/resp.14545) commentary in which Garun S. Hamilton, MBBS, PhD, and Bradley A. Edwards, PhD, underscored the nearly 1 billion people worldwide with OSA, most of whom are overweight or obese. “GLP-1 agonists are so effective that they have become a worldwide phenomenon. The high cost of the medications combined with the high prevalence of OSA means that there is no way that universal healthcare funding schemes can afford these medications, unless strict criteria are in place to prioritize those who can gain subsidized access and/or a duration of use limit is in place,” they stated. “This will no doubt exacerbate inequities in healthcare access and outcome between those from lower versus higher socioeconomic populations, as the attributable benefit from GLP-1 agonists is likely to be dependent on a patient’s ability to afford them.”
Beyond health equity concerns
The evidence for clinically relevant reductions in weight and resultant lowering of other adverse risk factors supports a wide embrace of Ozempic-type drugs. Standing alongside, however, are the cautionary pleas of nutrition/lifestyle-focused health advocates. They urge that prescriptions for nonpharmacological strategies that promote better sleep, healthier food choices, and more exercise need sharper highlighting and strong incentivizing.
Dr. Faiz said, “The availability and consumption of ultra-processed foods can impact food intake and weight. Specifically, in a small study of 20 inpatient adults admitted to the NIH Clinical Center randomized to either ultra-processed or unprocessed diets for 14 days, increased caloric intake and weight gain were found in the ultra-processed cohort.” In the study Dr. Faiz cited (doi: 10.1016/j.cmet.2019.05.008), meals were matched for calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Analysis showed a 4-pound weight difference between groups within 2 weeks: The ultra-processed cohort had taken in an extra 500 calories a day and had gained weight (0.9 ± 0.3 kg [P = .009]) and body fat while the unprocessed food group lost weight (0.9 ± 0.3 kg [P = .007]) and body fat.
“Thus, the type of foods we opt for can also have significant impact,” Dr. Faiz stated.
Dr. Faiz and Dr. Kuna said they had no conflicts of interest to disclose.
Will the weight reduction success with glucagon-like peptide-1 (GLP-1) agonists translate into strong reductions in obstructive sleep apnea (OSA)? Will those potential OSA benefits obviate the need in many for continuous positive airway pressure (CPAP)?
“I think it’s a game changer for helping people who are overweight or obese,” Samuel T. Kuna, MD, chief of sleep medicine at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, said in an interview with CHEST Physician. “I think we’re just starting out on a very exciting new era. We finally have quite effective treatments for this population.” Dr. Kuna’s Sleep AHEAD (Action for Health in Diabetes) 2021 study (doi: 10.1164/rccm.201912-2511OC) found that participants with OSA and type 2 diabetes mellitus receiving intensive lifestyle interventions for weight loss had reduced OSA severity at 10 years, and that OSA remission at 10 years was more common with intensive lifestyle intervention than with diabetes support and education.
Potential for OSA impact
In a JAMA Network Open/Pulmonary Medicine article on a 2022 study (doi: 10.1001/jamanetworkopen.2022.8212) conducted among 89 Spanish male adults with moderate to severe OSA and body mass index of 25 or greater, participants received CPAP therapy with or without 8 weeks of weight loss and lifestyle intervention. The primary endpoint of apnea-hypopnea index at 6 months showed the intervention to yield “clinically meaningful and sustainable improvements in OSA.”
Dr. Kuna stated, “I don’t think these [weight loss] agents eliminate the importance of behavioral modification, of changing diet, of reducing highly processed foods and maintaining a healthy lifestyle.” He acknowledged, however, that behavioral endeavors have been in general disappointing with respect to patients’ ability to achieve weight loss. “These medicines really open up a new strategy to help patients do that,” he added.
Dr. Kuna pointed to a recent (2023) Grunstein et al. perspective article (doi: 10.1093/sleep/zsad224) published in Sleep citing phase 3 trial results showing placebo-subtracted weight loss percentages. With subcutaneous (SC) semaglutide 2.4 mg they were 12.6% in patients with obesity or overweight with one or more weight-related comorbidities (but not type 2 diabetes), and 17.8% with tirzepatide (15 mg, SC, weekly), a combination GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, in a similar population. The authors stated, “These new agents, provided they are available to persons who need them most — who are often socioeconomically disadvantaged — could revolutionize the management of obesity and its many complications, including OSA.” Grunstein et al. also, noted that the number of studies showing improvement in cardiometabolic outcomes (eg, blood pressure) with pre-incretin OSA therapies are “minimal.” They underscored, however, the need for risk/benefit/cost-effectiveness data on incretin therapies, and cited evidence that withdrawal from incretin treatment brings back weight gain and adverse cardiometabolic factors. They also indicated key areas of uncertainty requiring research: gender-based response differences to incretins (women predominate in most weight loss studies, but OSA is more common in men), how CPAP users will adapt to incretin OSA benefits, direct comparisons of impact on OSA with incretins vs mechanical therapy, and understanding which target populations derive the most benefit with incretin therapies.
Despite the unanswered questions, the direction was unequivocally clear for Grunstein et al.: “Ultimately, the focus must shift away from mechanical therapy for obesity-related OSA towards weight loss, the latter which is likely to produce multiple health outcome improvements that are superior, including all-cause mortality.”
Dr. Kuna agreed with the Sleep article authors that one implication of this “incretin revolution” is that sleep physicians will have to broaden their skills to encompass obesity management. “As the field evolves, perhaps we should start training our fellows about how to manage these patients,” Dr. Kuna said.
Significant impact on OSA and CPAP
“Obesity is a risk factor for sleep apnea,” stated Saadia A. Faiz, MD, FCCP, professor, Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, “so with increased use of these GLP-1 agents for weight reduction, we would anticipate a significant impact on both OSA severity and need for CPAP.” Speaking in a CHEST Physician interview and referring to the Kuna et al. study, she stated, “Since cessation of the drug can lead to rebound weight gain, the emphasis on healthy eating and exercise is crucial to management.” Dr. Faiz said further, “It’s important to note that there are other weight-independent mechanisms for OSA, including upper airway anatomy, mechanisms that modulate upper airway stability, chemoreceptor sensitivity, visceral adiposity, neuroendocrine control, sleep quality, and other aspects of OSA pathophysiology yet to be discovered.”
Cost an obstacle for some
“For many insurances, criteria for coverage include obesity and prediabetes based on HbA1c. For some not meeting requirements, they will have to pay out of pocket,” Dr. Faiz said. She pointed to a Respirology (doi: 10.1111/resp.14545) commentary in which Garun S. Hamilton, MBBS, PhD, and Bradley A. Edwards, PhD, underscored the nearly 1 billion people worldwide with OSA, most of whom are overweight or obese. “GLP-1 agonists are so effective that they have become a worldwide phenomenon. The high cost of the medications combined with the high prevalence of OSA means that there is no way that universal healthcare funding schemes can afford these medications, unless strict criteria are in place to prioritize those who can gain subsidized access and/or a duration of use limit is in place,” they stated. “This will no doubt exacerbate inequities in healthcare access and outcome between those from lower versus higher socioeconomic populations, as the attributable benefit from GLP-1 agonists is likely to be dependent on a patient’s ability to afford them.”
Beyond health equity concerns
The evidence for clinically relevant reductions in weight and resultant lowering of other adverse risk factors supports a wide embrace of Ozempic-type drugs. Standing alongside, however, are the cautionary pleas of nutrition/lifestyle-focused health advocates. They urge that prescriptions for nonpharmacological strategies that promote better sleep, healthier food choices, and more exercise need sharper highlighting and strong incentivizing.
Dr. Faiz said, “The availability and consumption of ultra-processed foods can impact food intake and weight. Specifically, in a small study of 20 inpatient adults admitted to the NIH Clinical Center randomized to either ultra-processed or unprocessed diets for 14 days, increased caloric intake and weight gain were found in the ultra-processed cohort.” In the study Dr. Faiz cited (doi: 10.1016/j.cmet.2019.05.008), meals were matched for calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Analysis showed a 4-pound weight difference between groups within 2 weeks: The ultra-processed cohort had taken in an extra 500 calories a day and had gained weight (0.9 ± 0.3 kg [P = .009]) and body fat while the unprocessed food group lost weight (0.9 ± 0.3 kg [P = .007]) and body fat.
“Thus, the type of foods we opt for can also have significant impact,” Dr. Faiz stated.
Dr. Faiz and Dr. Kuna said they had no conflicts of interest to disclose.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Experts are voicing high hopes while citing important health equity concerns and reluctance to de-emphasize lifestyle remedies.</metaDescription> <articlePDF/> <teaserImage>301145</teaserImage> <teaser>Weight loss drugs, GLP-1s, could aid in obesity-related conditions such as OSA, but do not eliminate the need for lifestyle changes.</teaser> <title>Both Promise and Concern for OSA and CPAP with GLP-1s</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>2</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>chph</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">6</term> </publications> <sections> <term canonical="true">27980</term> </sections> <topics> <term canonical="true">296</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012858.jpg</altRep> <description role="drol:caption"/> <description role="drol:credit">Milleflore Images/Shutterstock</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400d5a9.jpg</altRep> <description role="drol:caption">Dr. Saadia A. Faiz</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Both Promise and Concern for OSA and CPAP with GLP-1s</title> <deck/> </itemMeta> <itemContent> <p>Will the weight reduction success with glucagon-like peptide-1 (GLP-1) agonists translate into strong reductions in obstructive sleep apnea (OSA)? Will those potential OSA benefits obviate the need in many for continuous positive airway pressure (CPAP)? <span class="tag metaDescription">Experts are voicing high hopes while citing important health equity concerns and reluctance to de-emphasize lifestyle remedies.</span> </p> <p>“I think it’s a game changer for helping people who are overweight or obese,” Samuel T. Kuna, MD, chief of sleep medicine at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, said in an interview with <em>CHEST Physician</em>. “I think we’re just starting out on a very exciting new era. We finally have quite effective treatments for this population.” Dr. Kuna’s Sleep AHEAD (Action for Health in Diabetes) 2021 study (<span class="Hyperlink"><a href="https://doi.org/10.1164/rccm.201912-2511OC">doi: 10.1164/rccm.201912-2511OC</a></span>) found that participants with OSA and type 2 diabetes mellitus receiving intensive lifestyle interventions for weight loss had reduced OSA severity at 10 years, and that OSA remission at 10 years was more common with intensive lifestyle intervention than with diabetes support and education.</p> <h2>Potential for OSA impact</h2> <p>In a <em>JAMA Network Open</em>/Pulmonary Medicine article on a 2022 study (<span class="id-label">doi: </span><span class="Hyperlink"><a href="https://doi.org/10.1001/jamanetworkopen.2022.8212">10.1001/jamanetworkopen.2022.8212</a></span><span class="identifier">)</span> conducted among 89 Spanish male adults with moderate to severe OSA and body mass index of 25 or greater, participants received CPAP therapy with or without 8 weeks of weight loss and lifestyle intervention. The primary endpoint of apnea-hypopnea index at 6 months showed the intervention to yield “clinically meaningful and sustainable improvements in OSA.”<br/><br/>Dr. Kuna stated, “I don’t think these [weight loss] agents eliminate the importance of behavioral modification, of changing diet, of reducing highly processed foods and maintaining a healthy lifestyle.” He acknowledged, however, that behavioral endeavors have been in general disappointing with respect to patients’ ability to achieve weight loss. “These medicines really open up a new strategy to help patients do that,” he added. [[{"fid":"301145","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Prescription for good health overhead","field_file_image_credit[und][0][value]":"Milleflore Images/Shutterstock","field_file_image_caption[und][0][value]":""},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>Dr. Kuna pointed to a recent (2023) Grunstein et al. perspective article (<span class="Hyperlink"><a href="https://doi.org/10.1093/sleep/zsad224">doi: 10.1093/sleep/zsad224</a></span>) published in <em>Sleep</em> citing phase 3 trial results showing placebo-subtracted weight loss percentages. With subcutaneous (SC) semaglutide 2.4 mg they were 12.6% in patients with obesity or overweight with one or more weight-related comorbidities (but not type 2 diabetes), and 17.8% with tirzepatide (15 mg, SC, weekly), a combination GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, in a similar population. The authors stated, “These new agents, provided they are available to persons who need them most — who are often socioeconomically disadvantaged — could revolutionize the management of obesity and its many complications, including OSA.” Grunstein et al. also, noted that the number of studies showing improvement in cardiometabolic outcomes (eg, blood pressure) with pre-incretin OSA therapies are “minimal.” They underscored, however, the need for risk/benefit/cost-effectiveness data on incretin therapies, and cited evidence that withdrawal from incretin treatment brings back weight gain and adverse cardiometabolic factors. They also indicated key areas of uncertainty requiring research: gender-based response differences to incretins (women predominate in most weight loss studies, but OSA is more common in men), how CPAP users will adapt to incretin OSA benefits, direct comparisons of impact on OSA with incretins vs mechanical therapy, and understanding which target populations derive the most benefit with incretin therapies. <br/><br/>Despite the unanswered questions, the direction was unequivocally clear for Grunstein et al.: “Ultimately, the focus must shift away from mechanical therapy for obesity-related OSA towards weight loss, the latter which is likely to produce multiple health outcome improvements that are superior, including all-cause mortality.” <br/><br/>Dr. Kuna agreed with the <em>Sleep</em> article authors that one implication of this “incretin revolution” is that sleep physicians will have to broaden their skills to encompass obesity management. “As the field evolves, perhaps we should start training our fellows about how to manage these patients,” Dr. Kuna said.<br/><br/></p> <h2>Significant impact on OSA and CPAP</h2> <p>“Obesity is a risk factor for sleep apnea,” stated Saadia A. Faiz, MD, FCCP, professor, Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, “so with increased use of these GLP-1 agents for weight reduction, we would anticipate a significant impact on both OSA severity and need for CPAP.” Speaking in a <em>CHEST Physician</em> interview and referring to the Kuna et al. study, she stated, “Since cessation of the drug can lead to rebound weight gain, the emphasis on healthy eating and exercise is crucial to management.” Dr. Faiz said further, “It’s important to note that there are other weight-independent mechanisms for OSA, including upper airway anatomy, mechanisms that modulate upper airway stability, chemoreceptor sensitivity, visceral adiposity, neuroendocrine control, sleep quality, and other aspects of OSA pathophysiology yet to be discovered.”[[{"fid":"256581","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Saadia A. Faiz, professor, Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Saadia A. Faiz"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/></p> <h2>Cost an obstacle for some</h2> <p>“For many insurances, criteria for coverage include obesity and prediabetes based on HbA1c. For some not meeting requirements, they will have to pay out of pocket,” Dr. Faiz said. She pointed to a <em>Respirology</em> (<span class="Hyperlink"><a href="https://doi.org/10.1111/resp.14545">doi: 10.1111/resp.14545</a></span>) commentary in which Garun S. Hamilton, MBBS, PhD, and Bradley A. Edwards, PhD, underscored the nearly 1 billion people worldwide with OSA, most of whom are overweight or obese. “GLP-1 agonists are so effective that they have become a worldwide phenomenon. The high cost of the medications combined with the high prevalence of OSA means that there is no way that universal healthcare funding schemes can afford these medications, unless strict criteria are in place to prioritize those who can gain subsidized access and/or a duration of use limit is in place,” they stated. “This will no doubt exacerbate inequities in healthcare access and outcome between those from lower versus higher socioeconomic populations, as the attributable benefit from GLP-1 agonists is likely to be dependent on a patient’s ability to afford them.”<br/><br/></p> <h2>Beyond health equity concerns</h2> <p>The evidence for clinically relevant reductions in weight and resultant lowering of other adverse risk factors supports a wide embrace of Ozempic-type drugs. Standing alongside, however, are the cautionary pleas of nutrition/lifestyle-focused health advocates. They urge that prescriptions for nonpharmacological strategies that promote better sleep, healthier food choices, and more exercise need sharper highlighting and strong incentivizing. <br/><br/>Dr. Faiz said, “The availability and consumption of ultra-processed foods can impact food intake and weight. Specifically, in a small study of 20 inpatient adults admitted to the NIH Clinical Center randomized to either ultra-processed or unprocessed diets for 14 days, increased caloric intake and weight gain were found in the ultra-processed cohort.” In the study Dr. Faiz cited (<span class="Hyperlink"><a href="https://doi.org/10.1016/j.cmet.2019.05.008">doi: 10.1016/j.cmet.2019.05.008</a></span>), meals were matched for calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Analysis showed a 4-pound weight difference between groups within 2 weeks: The ultra-processed cohort had taken in an extra 500 calories a day and had gained weight (0.9 ± 0.3 kg [<em>P</em> = .009]) and body fat while the unprocessed food group lost weight (0.9 ± 0.3 kg [<em>P</em> = .007]) and body fat. <br/><br/>“Thus, the type of foods we opt for can also have significant impact,” Dr. Faiz stated.<br/><br/>Dr. Faiz and Dr. Kuna said they had no conflicts of interest to disclose.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
