Neil Osterweil

SAN ANTONIO – Aromatase inhibitors, a mainstay of therapy in postmenopausal women with operable hormone receptor–positive breast cancers, are associated with reductions in endothelial function that could contribute to the development of cardiovascular disease, independent of the duration of therapy, investigators have found.

In a cross-sectional study examining endothelial function among postmenopausal women with locally advanced breast cancer on an aromatase inhibitor (AI), there were trends toward reduction in large and small artery elasticity and a significant decrement in vascular tone, compared with the vessels of healthy controls, reported Anne Blaes, MD, from the Masonic Cancer Center at the University of Minnesota in Minneapolis.

“Other studies have suggested that the cardiac risk from aromatase inhibitors is increased further in those with a previous diagnosis of cardiovascular disease. In this study we did not include this patient population, but I really think further work needs to be done in this area,” she said at the San Antonio Breast Cancer Symposium.

Her group’s findings suggest that prospective breast cancer trials need biomarkers to predict cardiovascular risk for patients who are on chronic AI therapy, she said.

CV incidence modest, deaths lows

The incidence rates of cardiovascular disease in clinical trials of adjuvant AI therapy have ranged from 3% to 17%, although the incidence of death from cardiovascular disease was relatively low in these trials, on the order of 1%-2%. Data on cardiovascular risk factors, however, were inconsistently collected across the various studies, Dr. Blaes noted.

“More recently, a lot of discussion has gone on about both the use of prolonged endocrine therapy using aromatase inhibitors – whether to consider 5 or 10 years – and in addition, as our population is aging, competing risks for mortality, whether that’s breast cancer or cardiovascular risk,” she said.

The investigators examined endothelial function in 36 postmenopausal women with locally advanced, operable breast cancer treated with curative intent with adjuvant AI therapy, and compared results with those of 25 healthy postmenopausal volunteers, five of whom were excluded from the final analysis due to prior use of exogenous estrogen.

About half of the patients had received chemotherapy, and two-thirds had received radiation therapy. The AIs used for most patients were anastrozole (Arimidex) and letrozole (Femara). Seven of the 36 cases had previously received tamoxifen.

The authors measured endothelial function using the EndoPAT (Itamar Medical) system that measures peripheral arterial tone (PAT) to identify reactive hyperemia. Endothelial dysfunction measured this way has been associated with an increased risk of cardiac adverse events independent of the Framingham Risk Score, Dr. Blaes said.

The participants underwent biomarker analysis and pulse wave analysis using a cardiovascular profiling system, and pulse contour analysis using the Endo-PAT2000 system. The investigators then compared biomarkers and functional test markers between cases and controls using T-tests and Wilcoxon Rank-Sum tests.

Biomarkers included inflammatory markers (high-sensitivity C-reactive protein, white blood cell count, interleukin 6), markers of hemostasis (fibrinogen, d-dimer, plasminogen-activator inhibitor-1, tissue-type plasminogen activator), and endothelial function markers (von Willebrand factor, circulating endothelial cells, soluble vascular cell adhesion molecule-1, and others).

They measured large-artery elasticity (LAE), small-artery elasticity (SAE), and the EndoPAT ratio, or reactive hyperemia index (RHI), the post-to-pre occlusion PAT signal ratio in the occluded side, normalized to the control side and further corrected for baseline vascular tone. An RHI score above 1.67 is considered normal, and a score of 1.67 or below is considered abnormal.

They found that both LAE and SAE trended toward significantly worse vascular tone in cases, compared with controls, but the differences were not statistically significant. The EndoPAT ratio, however, was significantly worse among cases, at 0.8, compared with 2.6 for controls, a difference that remained significant after controlling for systolic blood pressure (P less than .0001).

Hemostatic and endothelial biomarkers were significantly elevated in cases, compared with controls, but there were no significant differences in inflammatory markers.

When the investigators looked at the association between vascular function and cancer treatment characteristics, they found no differences in the use of chemotherapy, radiation, or left vs. right breast treated.

The use of anastrozole was associated with a significant reduction in LAE, compared with either letrozole or exemestane (P = .03). There was no association between duration of AI therapy and EndoPAT ratio.

Estradiol levels implicated

Not surprisingly, women on endocrine therapy in the study had significantly lower levels of estradiol than controls. Estradiol appears to be important for regulating healthy endothelial function, commented Patricia A. Ganz, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was the invited discussant.

“I think these are very provocative, hypothesis-generating findings, and I think they really fit what we expect the physiology should be in terms of endothelial function, even within this postmenopausal group of women where we’re looking at two discrete groups in terms of the estradiol level,” she said.

The study was funded by Building Interdisciplinary Research Careers in Women’s Health and a Masonic Scholar Award. Dr. Blaes and Dr. Ganz reported no relevant conflicts of interest.

SAN ANTONIO – Aromatase inhibitors, a mainstay of therapy in postmenopausal women with operable hormone receptor–positive breast cancers, are associated with reductions in endothelial function that could contribute to the development of cardiovascular disease, independent of the duration of therapy, investigators have found.

In a cross-sectional study examining endothelial function among postmenopausal women with locally advanced breast cancer on an aromatase inhibitor (AI), there were trends toward reduction in large and small artery elasticity and a significant decrement in vascular tone, compared with the vessels of healthy controls, reported Anne Blaes, MD, from the Masonic Cancer Center at the University of Minnesota in Minneapolis.

“Other studies have suggested that the cardiac risk from aromatase inhibitors is increased further in those with a previous diagnosis of cardiovascular disease. In this study we did not include this patient population, but I really think further work needs to be done in this area,” she said at the San Antonio Breast Cancer Symposium.

Her group’s findings suggest that prospective breast cancer trials need biomarkers to predict cardiovascular risk for patients who are on chronic AI therapy, she said.

CV incidence modest, deaths lows

The incidence rates of cardiovascular disease in clinical trials of adjuvant AI therapy have ranged from 3% to 17%, although the incidence of death from cardiovascular disease was relatively low in these trials, on the order of 1%-2%. Data on cardiovascular risk factors, however, were inconsistently collected across the various studies, Dr. Blaes noted.

“More recently, a lot of discussion has gone on about both the use of prolonged endocrine therapy using aromatase inhibitors – whether to consider 5 or 10 years – and in addition, as our population is aging, competing risks for mortality, whether that’s breast cancer or cardiovascular risk,” she said.

The investigators examined endothelial function in 36 postmenopausal women with locally advanced, operable breast cancer treated with curative intent with adjuvant AI therapy, and compared results with those of 25 healthy postmenopausal volunteers, five of whom were excluded from the final analysis due to prior use of exogenous estrogen.

About half of the patients had received chemotherapy, and two-thirds had received radiation therapy. The AIs used for most patients were anastrozole (Arimidex) and letrozole (Femara). Seven of the 36 cases had previously received tamoxifen.

The authors measured endothelial function using the EndoPAT (Itamar Medical) system that measures peripheral arterial tone (PAT) to identify reactive hyperemia. Endothelial dysfunction measured this way has been associated with an increased risk of cardiac adverse events independent of the Framingham Risk Score, Dr. Blaes said.

The participants underwent biomarker analysis and pulse wave analysis using a cardiovascular profiling system, and pulse contour analysis using the Endo-PAT2000 system. The investigators then compared biomarkers and functional test markers between cases and controls using T-tests and Wilcoxon Rank-Sum tests.

Biomarkers included inflammatory markers (high-sensitivity C-reactive protein, white blood cell count, interleukin 6), markers of hemostasis (fibrinogen, d-dimer, plasminogen-activator inhibitor-1, tissue-type plasminogen activator), and endothelial function markers (von Willebrand factor, circulating endothelial cells, soluble vascular cell adhesion molecule-1, and others).

They measured large-artery elasticity (LAE), small-artery elasticity (SAE), and the EndoPAT ratio, or reactive hyperemia index (RHI), the post-to-pre occlusion PAT signal ratio in the occluded side, normalized to the control side and further corrected for baseline vascular tone. An RHI score above 1.67 is considered normal, and a score of 1.67 or below is considered abnormal.

They found that both LAE and SAE trended toward significantly worse vascular tone in cases, compared with controls, but the differences were not statistically significant. The EndoPAT ratio, however, was significantly worse among cases, at 0.8, compared with 2.6 for controls, a difference that remained significant after controlling for systolic blood pressure (P less than .0001).

Hemostatic and endothelial biomarkers were significantly elevated in cases, compared with controls, but there were no significant differences in inflammatory markers.

When the investigators looked at the association between vascular function and cancer treatment characteristics, they found no differences in the use of chemotherapy, radiation, or left vs. right breast treated.

The use of anastrozole was associated with a significant reduction in LAE, compared with either letrozole or exemestane (P = .03). There was no association between duration of AI therapy and EndoPAT ratio.

Estradiol levels implicated

Not surprisingly, women on endocrine therapy in the study had significantly lower levels of estradiol than controls. Estradiol appears to be important for regulating healthy endothelial function, commented Patricia A. Ganz, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was the invited discussant.

“I think these are very provocative, hypothesis-generating findings, and I think they really fit what we expect the physiology should be in terms of endothelial function, even within this postmenopausal group of women where we’re looking at two discrete groups in terms of the estradiol level,” she said.

The study was funded by Building Interdisciplinary Research Careers in Women’s Health and a Masonic Scholar Award. Dr. Blaes and Dr. Ganz reported no relevant conflicts of interest.

SAN ANTONIO – Aromatase inhibitors, a mainstay of therapy in postmenopausal women with operable hormone receptor–positive breast cancers, are associated with reductions in endothelial function that could contribute to the development of cardiovascular disease, independent of the duration of therapy, investigators have found.

In a cross-sectional study examining endothelial function among postmenopausal women with locally advanced breast cancer on an aromatase inhibitor (AI), there were trends toward reduction in large and small artery elasticity and a significant decrement in vascular tone, compared with the vessels of healthy controls, reported Anne Blaes, MD, from the Masonic Cancer Center at the University of Minnesota in Minneapolis.

“Other studies have suggested that the cardiac risk from aromatase inhibitors is increased further in those with a previous diagnosis of cardiovascular disease. In this study we did not include this patient population, but I really think further work needs to be done in this area,” she said at the San Antonio Breast Cancer Symposium.

Her group’s findings suggest that prospective breast cancer trials need biomarkers to predict cardiovascular risk for patients who are on chronic AI therapy, she said.

CV incidence modest, deaths lows

The incidence rates of cardiovascular disease in clinical trials of adjuvant AI therapy have ranged from 3% to 17%, although the incidence of death from cardiovascular disease was relatively low in these trials, on the order of 1%-2%. Data on cardiovascular risk factors, however, were inconsistently collected across the various studies, Dr. Blaes noted.

“More recently, a lot of discussion has gone on about both the use of prolonged endocrine therapy using aromatase inhibitors – whether to consider 5 or 10 years – and in addition, as our population is aging, competing risks for mortality, whether that’s breast cancer or cardiovascular risk,” she said.

The investigators examined endothelial function in 36 postmenopausal women with locally advanced, operable breast cancer treated with curative intent with adjuvant AI therapy, and compared results with those of 25 healthy postmenopausal volunteers, five of whom were excluded from the final analysis due to prior use of exogenous estrogen.

About half of the patients had received chemotherapy, and two-thirds had received radiation therapy. The AIs used for most patients were anastrozole (Arimidex) and letrozole (Femara). Seven of the 36 cases had previously received tamoxifen.

The authors measured endothelial function using the EndoPAT (Itamar Medical) system that measures peripheral arterial tone (PAT) to identify reactive hyperemia. Endothelial dysfunction measured this way has been associated with an increased risk of cardiac adverse events independent of the Framingham Risk Score, Dr. Blaes said.

The participants underwent biomarker analysis and pulse wave analysis using a cardiovascular profiling system, and pulse contour analysis using the Endo-PAT2000 system. The investigators then compared biomarkers and functional test markers between cases and controls using T-tests and Wilcoxon Rank-Sum tests.

Biomarkers included inflammatory markers (high-sensitivity C-reactive protein, white blood cell count, interleukin 6), markers of hemostasis (fibrinogen, d-dimer, plasminogen-activator inhibitor-1, tissue-type plasminogen activator), and endothelial function markers (von Willebrand factor, circulating endothelial cells, soluble vascular cell adhesion molecule-1, and others).

They measured large-artery elasticity (LAE), small-artery elasticity (SAE), and the EndoPAT ratio, or reactive hyperemia index (RHI), the post-to-pre occlusion PAT signal ratio in the occluded side, normalized to the control side and further corrected for baseline vascular tone. An RHI score above 1.67 is considered normal, and a score of 1.67 or below is considered abnormal.

They found that both LAE and SAE trended toward significantly worse vascular tone in cases, compared with controls, but the differences were not statistically significant. The EndoPAT ratio, however, was significantly worse among cases, at 0.8, compared with 2.6 for controls, a difference that remained significant after controlling for systolic blood pressure (P less than .0001).

Hemostatic and endothelial biomarkers were significantly elevated in cases, compared with controls, but there were no significant differences in inflammatory markers.

When the investigators looked at the association between vascular function and cancer treatment characteristics, they found no differences in the use of chemotherapy, radiation, or left vs. right breast treated.

The use of anastrozole was associated with a significant reduction in LAE, compared with either letrozole or exemestane (P = .03). There was no association between duration of AI therapy and EndoPAT ratio.

Estradiol levels implicated

Not surprisingly, women on endocrine therapy in the study had significantly lower levels of estradiol than controls. Estradiol appears to be important for regulating healthy endothelial function, commented Patricia A. Ganz, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was the invited discussant.

“I think these are very provocative, hypothesis-generating findings, and I think they really fit what we expect the physiology should be in terms of endothelial function, even within this postmenopausal group of women where we’re looking at two discrete groups in terms of the estradiol level,” she said.

The study was funded by Building Interdisciplinary Research Careers in Women’s Health and a Masonic Scholar Award. Dr. Blaes and Dr. Ganz reported no relevant conflicts of interest.

SAN ANTONIO – Although adding concurrent estrogen deprivation to a standard combination chemotherapy regimen for women with breast cancers positive for the estrogen receptors (ER+) and the human epidermal growth factor receptor–2 (HER2+) did not add to the already considerable toxicity, it also did not seem to add much benefit, according to an investigator in the NSABP B-52 trial.

Among 311 women with ER+/HER2+ tumors randomized to neoadjuvant therapy with docetaxel, carboplatin, trastuzumab (Herceptin), and pertuzumab (Perjeta) with or without estrogen deprivation therapy, there was no statistically significant difference in the primary endpoint of pathologic complete response (pCR) rates, reported Mothaffar F. Rimawi, MD, of the breast center at Baylor College of Medicine in Houston.

Rimawi_Mothaffar_F_web.JPG

Endocrine/chemo interplay?

The rationale for the trial was based on several previous findings, including the propensity for ER+/HER2+ tumors to be less responsive to dual anti-HER2 therapy with trastuzumab (Herceptin) and pertuzumab (Perjeta).

There is also evidence to suggest that the estrogen receptor may act as a pathway of resistance to anti-HER2 therapy, and evidence from older trials suggested that chemotherapy and endocrine therapy may have antagonistic effects, he said.

The investigators hypothesized that concurrent inhibition of ER and HER2 tumors with neoadjuvant chemotherapy consisting of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) would not be antagonistic, and could overcome resistance to treatment as shown by improvements in pathologic complete response rates.

The investigators enrolled women with HER+ and ER+ and/or progresterone receptor–positive (PR+) invasive breast cancer diagnosed by core needle biopsy, stratified them by premenopausal or postmenopausal status, and then randomized them to receive chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab every 21 days for six cycles, with or without estrogen deprivation therapy. Postmenopausal women received an aromatase inhibitor, and premenopausal women received an aromatase inhibitor plus ovarian suppression with goserelin and a lutenizing hormone–releasing hormone agonist.

For the primary endpoint, overall rates of pCR in the breast and nodes were 41% among 154 patients treated with TCHP chemotherapy alone, vs. 46% for 157 women treated with TCHP and estrogen deprivation, a difference that was not statistically significant. The results were similar in an analysis stratified by menopausal status: 44% vs. 46%, respectively, in premenopausal women, and 38% vs. 45% in postmenopausal women. Neither comparison was statistically significant.

In addition, no overall or stratified differences were seen in terms of pCR in the breast alone, and no differences were seen in clinical complete response rates, at 68.1% vs. 73.9%, respectively.

Nearly 100% of patients in the TCHP chemotherapy alone arm had diarrhea, ranging from 42% with grade 1, to 34% with grade 2, to 23% with grade 3, to less than 1% with grade 4. The distribution of diarrhea severity was virtually identical among patients treated with TCHP plus estrogen deprivation, all of whom experienced some grade. Other common gastrointestinal side effects in each study arm included nausea, vomiting, and dehydration, occurring in nearly all patients with equal distribution of severity between the two arms.

Hematologic toxicities included anemia, hypokalemia, and febrile neutropenia, again distributed evenly in severity between the trial arms.

Alternative endpoint?

Dr. Rimawi said the pCR endpoint commonly used in clinical trials may not be ideal for studying therapy in this population, because it generally correlates with outcomes among women when tumors are ER negative,“but when they are ER positive, the absence of a pathologic complete response is not necessarily a bad thing.”

He said that residual cancer burden, or RCB, appears to be a better marker for prognosis than pCR in patients with ER+/HER2+ tumors.

“In this population we need a different metric, a metric that is not path CR,” agreed Carlos Arteaga, MD, professor of cancer biology and medicine, and coleader of the breast cancer research program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

“We need other metrics that are more objective and more correlated with long-term outcomes. Path CR is not,” said Dr. Arteaga, who moderated a briefing where NSABP B-52 data were discussed prior to their presentation in the general session.

Regarding the lack of statistical significance, Dr. Rimawi said it is possible that the effects of chemotherapy may have blunted the responses that might otherwise have been seen with the addition of estrogen deprivation.

“We believe that if we de-escalate treatment, we could see a higher response to the estrogen receptor inhibitor,” he said.

NSABP B-52 was supported by the National Cancer Institute and Genentech. Dr. Rimawi reported contracted research from Genentech and GlaxoSmithKline. Dr. Arteaga reported no disclosures relevant to the trial.

SAN ANTONIO – Although adding concurrent estrogen deprivation to a standard combination chemotherapy regimen for women with breast cancers positive for the estrogen receptors (ER+) and the human epidermal growth factor receptor–2 (HER2+) did not add to the already considerable toxicity, it also did not seem to add much benefit, according to an investigator in the NSABP B-52 trial.

Among 311 women with ER+/HER2+ tumors randomized to neoadjuvant therapy with docetaxel, carboplatin, trastuzumab (Herceptin), and pertuzumab (Perjeta) with or without estrogen deprivation therapy, there was no statistically significant difference in the primary endpoint of pathologic complete response (pCR) rates, reported Mothaffar F. Rimawi, MD, of the breast center at Baylor College of Medicine in Houston.

Rimawi_Mothaffar_F_web.JPG

Endocrine/chemo interplay?

The rationale for the trial was based on several previous findings, including the propensity for ER+/HER2+ tumors to be less responsive to dual anti-HER2 therapy with trastuzumab (Herceptin) and pertuzumab (Perjeta).

There is also evidence to suggest that the estrogen receptor may act as a pathway of resistance to anti-HER2 therapy, and evidence from older trials suggested that chemotherapy and endocrine therapy may have antagonistic effects, he said.

The investigators hypothesized that concurrent inhibition of ER and HER2 tumors with neoadjuvant chemotherapy consisting of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) would not be antagonistic, and could overcome resistance to treatment as shown by improvements in pathologic complete response rates.

The investigators enrolled women with HER+ and ER+ and/or progresterone receptor–positive (PR+) invasive breast cancer diagnosed by core needle biopsy, stratified them by premenopausal or postmenopausal status, and then randomized them to receive chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab every 21 days for six cycles, with or without estrogen deprivation therapy. Postmenopausal women received an aromatase inhibitor, and premenopausal women received an aromatase inhibitor plus ovarian suppression with goserelin and a lutenizing hormone–releasing hormone agonist.

For the primary endpoint, overall rates of pCR in the breast and nodes were 41% among 154 patients treated with TCHP chemotherapy alone, vs. 46% for 157 women treated with TCHP and estrogen deprivation, a difference that was not statistically significant. The results were similar in an analysis stratified by menopausal status: 44% vs. 46%, respectively, in premenopausal women, and 38% vs. 45% in postmenopausal women. Neither comparison was statistically significant.

In addition, no overall or stratified differences were seen in terms of pCR in the breast alone, and no differences were seen in clinical complete response rates, at 68.1% vs. 73.9%, respectively.

Nearly 100% of patients in the TCHP chemotherapy alone arm had diarrhea, ranging from 42% with grade 1, to 34% with grade 2, to 23% with grade 3, to less than 1% with grade 4. The distribution of diarrhea severity was virtually identical among patients treated with TCHP plus estrogen deprivation, all of whom experienced some grade. Other common gastrointestinal side effects in each study arm included nausea, vomiting, and dehydration, occurring in nearly all patients with equal distribution of severity between the two arms.

Hematologic toxicities included anemia, hypokalemia, and febrile neutropenia, again distributed evenly in severity between the trial arms.

Alternative endpoint?

Dr. Rimawi said the pCR endpoint commonly used in clinical trials may not be ideal for studying therapy in this population, because it generally correlates with outcomes among women when tumors are ER negative,“but when they are ER positive, the absence of a pathologic complete response is not necessarily a bad thing.”

He said that residual cancer burden, or RCB, appears to be a better marker for prognosis than pCR in patients with ER+/HER2+ tumors.

“In this population we need a different metric, a metric that is not path CR,” agreed Carlos Arteaga, MD, professor of cancer biology and medicine, and coleader of the breast cancer research program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

“We need other metrics that are more objective and more correlated with long-term outcomes. Path CR is not,” said Dr. Arteaga, who moderated a briefing where NSABP B-52 data were discussed prior to their presentation in the general session.

Regarding the lack of statistical significance, Dr. Rimawi said it is possible that the effects of chemotherapy may have blunted the responses that might otherwise have been seen with the addition of estrogen deprivation.

“We believe that if we de-escalate treatment, we could see a higher response to the estrogen receptor inhibitor,” he said.

NSABP B-52 was supported by the National Cancer Institute and Genentech. Dr. Rimawi reported contracted research from Genentech and GlaxoSmithKline. Dr. Arteaga reported no disclosures relevant to the trial.

SAN ANTONIO – Although adding concurrent estrogen deprivation to a standard combination chemotherapy regimen for women with breast cancers positive for the estrogen receptors (ER+) and the human epidermal growth factor receptor–2 (HER2+) did not add to the already considerable toxicity, it also did not seem to add much benefit, according to an investigator in the NSABP B-52 trial.

Among 311 women with ER+/HER2+ tumors randomized to neoadjuvant therapy with docetaxel, carboplatin, trastuzumab (Herceptin), and pertuzumab (Perjeta) with or without estrogen deprivation therapy, there was no statistically significant difference in the primary endpoint of pathologic complete response (pCR) rates, reported Mothaffar F. Rimawi, MD, of the breast center at Baylor College of Medicine in Houston.

Rimawi_Mothaffar_F_web.JPG

Endocrine/chemo interplay?

The rationale for the trial was based on several previous findings, including the propensity for ER+/HER2+ tumors to be less responsive to dual anti-HER2 therapy with trastuzumab (Herceptin) and pertuzumab (Perjeta).

There is also evidence to suggest that the estrogen receptor may act as a pathway of resistance to anti-HER2 therapy, and evidence from older trials suggested that chemotherapy and endocrine therapy may have antagonistic effects, he said.

The investigators hypothesized that concurrent inhibition of ER and HER2 tumors with neoadjuvant chemotherapy consisting of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) would not be antagonistic, and could overcome resistance to treatment as shown by improvements in pathologic complete response rates.

The investigators enrolled women with HER+ and ER+ and/or progresterone receptor–positive (PR+) invasive breast cancer diagnosed by core needle biopsy, stratified them by premenopausal or postmenopausal status, and then randomized them to receive chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab every 21 days for six cycles, with or without estrogen deprivation therapy. Postmenopausal women received an aromatase inhibitor, and premenopausal women received an aromatase inhibitor plus ovarian suppression with goserelin and a lutenizing hormone–releasing hormone agonist.

For the primary endpoint, overall rates of pCR in the breast and nodes were 41% among 154 patients treated with TCHP chemotherapy alone, vs. 46% for 157 women treated with TCHP and estrogen deprivation, a difference that was not statistically significant. The results were similar in an analysis stratified by menopausal status: 44% vs. 46%, respectively, in premenopausal women, and 38% vs. 45% in postmenopausal women. Neither comparison was statistically significant.

In addition, no overall or stratified differences were seen in terms of pCR in the breast alone, and no differences were seen in clinical complete response rates, at 68.1% vs. 73.9%, respectively.

Nearly 100% of patients in the TCHP chemotherapy alone arm had diarrhea, ranging from 42% with grade 1, to 34% with grade 2, to 23% with grade 3, to less than 1% with grade 4. The distribution of diarrhea severity was virtually identical among patients treated with TCHP plus estrogen deprivation, all of whom experienced some grade. Other common gastrointestinal side effects in each study arm included nausea, vomiting, and dehydration, occurring in nearly all patients with equal distribution of severity between the two arms.

Hematologic toxicities included anemia, hypokalemia, and febrile neutropenia, again distributed evenly in severity between the trial arms.

Alternative endpoint?

Dr. Rimawi said the pCR endpoint commonly used in clinical trials may not be ideal for studying therapy in this population, because it generally correlates with outcomes among women when tumors are ER negative,“but when they are ER positive, the absence of a pathologic complete response is not necessarily a bad thing.”

He said that residual cancer burden, or RCB, appears to be a better marker for prognosis than pCR in patients with ER+/HER2+ tumors.

“In this population we need a different metric, a metric that is not path CR,” agreed Carlos Arteaga, MD, professor of cancer biology and medicine, and coleader of the breast cancer research program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

“We need other metrics that are more objective and more correlated with long-term outcomes. Path CR is not,” said Dr. Arteaga, who moderated a briefing where NSABP B-52 data were discussed prior to their presentation in the general session.

Regarding the lack of statistical significance, Dr. Rimawi said it is possible that the effects of chemotherapy may have blunted the responses that might otherwise have been seen with the addition of estrogen deprivation.

“We believe that if we de-escalate treatment, we could see a higher response to the estrogen receptor inhibitor,” he said.

NSABP B-52 was supported by the National Cancer Institute and Genentech. Dr. Rimawi reported contracted research from Genentech and GlaxoSmithKline. Dr. Arteaga reported no disclosures relevant to the trial.

SAN ANTONIO – Breast cancers that are positive for the estrogen receptor (ER) and human epidermal growth factor receptor–2 (HER2) are less likely than ER-negative/HER2-positive tumors to respond to dual anti-HER2 therapy, suggesting that the estrogen receptor may act as a pathway of resistance to anti-HER2 treatment.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-52 trial was designed to test the hypothesis that concurrent inhibition of both ER and HER2 added to chemotherapy with a platinum compound and a taxane will overcome resistance to treatment and improve pathologic complete response (pCR) rates in patients with ER-positive/HER2-positive breast cancer.

In a video interview at the San Antonio Breast Cancer Symposium, Mothaffar F. Rimawi, MD, discusses the trial results, which failed to show a significant difference in pCR rates between women who received chemotherapy with estrogen deprivation or chemotherapy alone. However, the trial still provided important information about the interplay between hormonal and HER2 receptors, and may inform future clinical trials examining reduction in tumor burden as a prognostic measure, says Dr. Rimawi from the Breast Center at Baylor College of Medicine, Houston.

op@frontlinemedcom.com

SAN ANTONIO – Breast cancers that are positive for the estrogen receptor (ER) and human epidermal growth factor receptor–2 (HER2) are less likely than ER-negative/HER2-positive tumors to respond to dual anti-HER2 therapy, suggesting that the estrogen receptor may act as a pathway of resistance to anti-HER2 treatment.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-52 trial was designed to test the hypothesis that concurrent inhibition of both ER and HER2 added to chemotherapy with a platinum compound and a taxane will overcome resistance to treatment and improve pathologic complete response (pCR) rates in patients with ER-positive/HER2-positive breast cancer.

In a video interview at the San Antonio Breast Cancer Symposium, Mothaffar F. Rimawi, MD, discusses the trial results, which failed to show a significant difference in pCR rates between women who received chemotherapy with estrogen deprivation or chemotherapy alone. However, the trial still provided important information about the interplay between hormonal and HER2 receptors, and may inform future clinical trials examining reduction in tumor burden as a prognostic measure, says Dr. Rimawi from the Breast Center at Baylor College of Medicine, Houston.

op@frontlinemedcom.com

SAN ANTONIO – Breast cancers that are positive for the estrogen receptor (ER) and human epidermal growth factor receptor–2 (HER2) are less likely than ER-negative/HER2-positive tumors to respond to dual anti-HER2 therapy, suggesting that the estrogen receptor may act as a pathway of resistance to anti-HER2 treatment.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-52 trial was designed to test the hypothesis that concurrent inhibition of both ER and HER2 added to chemotherapy with a platinum compound and a taxane will overcome resistance to treatment and improve pathologic complete response (pCR) rates in patients with ER-positive/HER2-positive breast cancer.

In a video interview at the San Antonio Breast Cancer Symposium, Mothaffar F. Rimawi, MD, discusses the trial results, which failed to show a significant difference in pCR rates between women who received chemotherapy with estrogen deprivation or chemotherapy alone. However, the trial still provided important information about the interplay between hormonal and HER2 receptors, and may inform future clinical trials examining reduction in tumor burden as a prognostic measure, says Dr. Rimawi from the Breast Center at Baylor College of Medicine, Houston.

op@frontlinemedcom.com

SAN ANTONIO – When does adjuvant therapy with an aromatase inhibitor become too much of a good thing? Or to put it another way, what’s the optimal duration of extended aromatase inhibitor therapy? That’s the question that three clinical trials have tried – but largely failed – to answer.

For example, the randomized, double-blinded NSABP B-42 trial, comparing extended therapy with letrozole (Femara) in postmenopausal women with hormone receptor–positive (HR+) breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) showed no difference in disease-free survival (DFS) after 7 years of follow-up between women treated with extended letrozole or placebo.

Mamounas_Eleftherios_P_web.jpg

DATA data

In the DATA study, also presented here, investigators from the Netherlands compared 6 years of anastrozole (Arimidex) to 3 years of anastrozole following 2 or 3 years of adjuvant tamoxifen for postmenopausal women with estrogen receptor–positive (ER+), and/or progesterone receptor–positive (PR+) breast cancer.

They found that “adapted” DFS (DFS starting 3 years after randomization) and adapted overall survival (OS) were similar between the two groups.

“The findings of the DATA study do not support extended adjuvant AI use after 5 years of sequential endocrine therapy for all postmenopausal hormone receptor–positive breast cancer patients,” said Vivianne Tjan-Heijnen, MD, of Maastricht University Medical Center in the Netherlands.

Less than ideal

In the optimistically named IDEAL trial, a separate team of investigators, also from the Netherlands, looked at the relative merits of continuing adjuvant therapy with letrozole for 2.5 or 5 years following 5 years of adjuvant therapy with tamoxifen, an AI, or a combination in postmenopausal women with HR+ breast cancer.

They found no differences in either DFS or OS between patients treated for 5 years or those treated for only half that long.

“We conclude that there is no benefit of extending AI-based therapy longer than two-and-a-half years,” said Erik Blok, MD, of Leiden University Medical Center in the Netherlands.

Give what to whom for how long?

Results of the trials raise more questions than they answer, said Michael Gnant, MD, of the Medical University of Vienna, the invited discussant.

“Essentially, these three trials did not reach the necessary statistical significance levels to demonstrate a clear benefit for the respective AI extension,” he said.

“Can other agents we use in luminal breast cancer help? Frankly, I don’t think so. Based on their tolerability profile, and in part also on financial toxicity, I don’t think that the promising agents we explore in many situations for the treatment of hormone receptor–positive breast cancer will realistically be used in the extended adjuvant setting,” he said.

What’s needed, he said, are new strategies for targeting the chronic part of luminal breast cancer recurrence risk. Using endocrine therapies in this setting will likely be ineffective. Instead, agents that could directly target dormant cancer stem cells would “eliminate the source of late metastases for good.”

The best evidence to date clearly points to individualized treatment plans for patients, Dr. Gnant said.

For example, for a patient who has had 2-5 years of tamoxifen, an AI for 2.5-5 additional years can help to prevent recurrences, provided that the patient has risk factors for recurrence and excellent bone health.

“Based on the trial results, it is more complex for a patient who comes off initial or sequential AI. There are factors favoring the extension of AI treatment, and other factors to speak against such extension. I suggest to start with patient features at this time,” he said.

Currently, the main factor driving the choice of extended AI therapy will be how well the patient has tolerated AIs in the first years of therapy and whether she is at increased risk for fractures, suggesting younger age as a factor favoring extended AI use.

Patients with higher clinicopathologic risk factors such as node positivity or more luminal type tumors, as well as higher risk according to genomic studies, might also benefit from extended AI therapy, he said.

Biomarkers needed

“What the data from these and other trials tell us is that endocrine therapy is not for everyone. We need biomarkers that can tell us who should be getting extended endocrine therapy, be it 10 years or even a longer duration of time, versus a subgroup that might do very well with 5 five years of AI,” Aditya Bardia, MBBS, MPH, of the breast cancer division at Massachusetts General Hospital Cancer Center in Boston, said in an interview.

There are several such biomarkers under investigation, but they need validation and testing in large scale clinical trials before they find their way into day-to-practice, he said.

Dr. Bardia was not involved in the studies.

NSABP B-42 was sponsored by PrECOG with financial support from Novartis. Dr. Mamounas reported having no conflicts of interest. The DATA trial was sponsored by the Dutch Breast Cancer Research Group and Novartis. Dr. Tjan-Heijnen reported nothing to disclose. IDEAL was supported by the Dutch Breast Cancer Research Group and Novartis. Dr. Blok reported nothing to disclose.

SAN ANTONIO – When does adjuvant therapy with an aromatase inhibitor become too much of a good thing? Or to put it another way, what’s the optimal duration of extended aromatase inhibitor therapy? That’s the question that three clinical trials have tried – but largely failed – to answer.

For example, the randomized, double-blinded NSABP B-42 trial, comparing extended therapy with letrozole (Femara) in postmenopausal women with hormone receptor–positive (HR+) breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) showed no difference in disease-free survival (DFS) after 7 years of follow-up between women treated with extended letrozole or placebo.

Mamounas_Eleftherios_P_web.jpg

DATA data

In the DATA study, also presented here, investigators from the Netherlands compared 6 years of anastrozole (Arimidex) to 3 years of anastrozole following 2 or 3 years of adjuvant tamoxifen for postmenopausal women with estrogen receptor–positive (ER+), and/or progesterone receptor–positive (PR+) breast cancer.

They found that “adapted” DFS (DFS starting 3 years after randomization) and adapted overall survival (OS) were similar between the two groups.

“The findings of the DATA study do not support extended adjuvant AI use after 5 years of sequential endocrine therapy for all postmenopausal hormone receptor–positive breast cancer patients,” said Vivianne Tjan-Heijnen, MD, of Maastricht University Medical Center in the Netherlands.

Less than ideal

In the optimistically named IDEAL trial, a separate team of investigators, also from the Netherlands, looked at the relative merits of continuing adjuvant therapy with letrozole for 2.5 or 5 years following 5 years of adjuvant therapy with tamoxifen, an AI, or a combination in postmenopausal women with HR+ breast cancer.

They found no differences in either DFS or OS between patients treated for 5 years or those treated for only half that long.

“We conclude that there is no benefit of extending AI-based therapy longer than two-and-a-half years,” said Erik Blok, MD, of Leiden University Medical Center in the Netherlands.

Give what to whom for how long?

Results of the trials raise more questions than they answer, said Michael Gnant, MD, of the Medical University of Vienna, the invited discussant.

“Essentially, these three trials did not reach the necessary statistical significance levels to demonstrate a clear benefit for the respective AI extension,” he said.

“Can other agents we use in luminal breast cancer help? Frankly, I don’t think so. Based on their tolerability profile, and in part also on financial toxicity, I don’t think that the promising agents we explore in many situations for the treatment of hormone receptor–positive breast cancer will realistically be used in the extended adjuvant setting,” he said.

What’s needed, he said, are new strategies for targeting the chronic part of luminal breast cancer recurrence risk. Using endocrine therapies in this setting will likely be ineffective. Instead, agents that could directly target dormant cancer stem cells would “eliminate the source of late metastases for good.”

The best evidence to date clearly points to individualized treatment plans for patients, Dr. Gnant said.

For example, for a patient who has had 2-5 years of tamoxifen, an AI for 2.5-5 additional years can help to prevent recurrences, provided that the patient has risk factors for recurrence and excellent bone health.

“Based on the trial results, it is more complex for a patient who comes off initial or sequential AI. There are factors favoring the extension of AI treatment, and other factors to speak against such extension. I suggest to start with patient features at this time,” he said.

Currently, the main factor driving the choice of extended AI therapy will be how well the patient has tolerated AIs in the first years of therapy and whether she is at increased risk for fractures, suggesting younger age as a factor favoring extended AI use.

Patients with higher clinicopathologic risk factors such as node positivity or more luminal type tumors, as well as higher risk according to genomic studies, might also benefit from extended AI therapy, he said.

Biomarkers needed

“What the data from these and other trials tell us is that endocrine therapy is not for everyone. We need biomarkers that can tell us who should be getting extended endocrine therapy, be it 10 years or even a longer duration of time, versus a subgroup that might do very well with 5 five years of AI,” Aditya Bardia, MBBS, MPH, of the breast cancer division at Massachusetts General Hospital Cancer Center in Boston, said in an interview.

There are several such biomarkers under investigation, but they need validation and testing in large scale clinical trials before they find their way into day-to-practice, he said.

Dr. Bardia was not involved in the studies.

NSABP B-42 was sponsored by PrECOG with financial support from Novartis. Dr. Mamounas reported having no conflicts of interest. The DATA trial was sponsored by the Dutch Breast Cancer Research Group and Novartis. Dr. Tjan-Heijnen reported nothing to disclose. IDEAL was supported by the Dutch Breast Cancer Research Group and Novartis. Dr. Blok reported nothing to disclose.

SAN ANTONIO – When does adjuvant therapy with an aromatase inhibitor become too much of a good thing? Or to put it another way, what’s the optimal duration of extended aromatase inhibitor therapy? That’s the question that three clinical trials have tried – but largely failed – to answer.

For example, the randomized, double-blinded NSABP B-42 trial, comparing extended therapy with letrozole (Femara) in postmenopausal women with hormone receptor–positive (HR+) breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) showed no difference in disease-free survival (DFS) after 7 years of follow-up between women treated with extended letrozole or placebo.

Mamounas_Eleftherios_P_web.jpg

DATA data

In the DATA study, also presented here, investigators from the Netherlands compared 6 years of anastrozole (Arimidex) to 3 years of anastrozole following 2 or 3 years of adjuvant tamoxifen for postmenopausal women with estrogen receptor–positive (ER+), and/or progesterone receptor–positive (PR+) breast cancer.

They found that “adapted” DFS (DFS starting 3 years after randomization) and adapted overall survival (OS) were similar between the two groups.

“The findings of the DATA study do not support extended adjuvant AI use after 5 years of sequential endocrine therapy for all postmenopausal hormone receptor–positive breast cancer patients,” said Vivianne Tjan-Heijnen, MD, of Maastricht University Medical Center in the Netherlands.

Less than ideal

In the optimistically named IDEAL trial, a separate team of investigators, also from the Netherlands, looked at the relative merits of continuing adjuvant therapy with letrozole for 2.5 or 5 years following 5 years of adjuvant therapy with tamoxifen, an AI, or a combination in postmenopausal women with HR+ breast cancer.

They found no differences in either DFS or OS between patients treated for 5 years or those treated for only half that long.

“We conclude that there is no benefit of extending AI-based therapy longer than two-and-a-half years,” said Erik Blok, MD, of Leiden University Medical Center in the Netherlands.

Give what to whom for how long?

Results of the trials raise more questions than they answer, said Michael Gnant, MD, of the Medical University of Vienna, the invited discussant.

“Essentially, these three trials did not reach the necessary statistical significance levels to demonstrate a clear benefit for the respective AI extension,” he said.

“Can other agents we use in luminal breast cancer help? Frankly, I don’t think so. Based on their tolerability profile, and in part also on financial toxicity, I don’t think that the promising agents we explore in many situations for the treatment of hormone receptor–positive breast cancer will realistically be used in the extended adjuvant setting,” he said.

What’s needed, he said, are new strategies for targeting the chronic part of luminal breast cancer recurrence risk. Using endocrine therapies in this setting will likely be ineffective. Instead, agents that could directly target dormant cancer stem cells would “eliminate the source of late metastases for good.”

The best evidence to date clearly points to individualized treatment plans for patients, Dr. Gnant said.

For example, for a patient who has had 2-5 years of tamoxifen, an AI for 2.5-5 additional years can help to prevent recurrences, provided that the patient has risk factors for recurrence and excellent bone health.

“Based on the trial results, it is more complex for a patient who comes off initial or sequential AI. There are factors favoring the extension of AI treatment, and other factors to speak against such extension. I suggest to start with patient features at this time,” he said.

Currently, the main factor driving the choice of extended AI therapy will be how well the patient has tolerated AIs in the first years of therapy and whether she is at increased risk for fractures, suggesting younger age as a factor favoring extended AI use.

Patients with higher clinicopathologic risk factors such as node positivity or more luminal type tumors, as well as higher risk according to genomic studies, might also benefit from extended AI therapy, he said.

Biomarkers needed

“What the data from these and other trials tell us is that endocrine therapy is not for everyone. We need biomarkers that can tell us who should be getting extended endocrine therapy, be it 10 years or even a longer duration of time, versus a subgroup that might do very well with 5 five years of AI,” Aditya Bardia, MBBS, MPH, of the breast cancer division at Massachusetts General Hospital Cancer Center in Boston, said in an interview.

There are several such biomarkers under investigation, but they need validation and testing in large scale clinical trials before they find their way into day-to-practice, he said.

Dr. Bardia was not involved in the studies.

NSABP B-42 was sponsored by PrECOG with financial support from Novartis. Dr. Mamounas reported having no conflicts of interest. The DATA trial was sponsored by the Dutch Breast Cancer Research Group and Novartis. Dr. Tjan-Heijnen reported nothing to disclose. IDEAL was supported by the Dutch Breast Cancer Research Group and Novartis. Dr. Blok reported nothing to disclose.

SAN ANTONIO – Adding everolimus to fulvestrant doubled median progression-free survival among postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer resistant to therapy with an aromatase inhibitor [AI] in the PrECOG 0102 study.

In the randomized phase II trial, the combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) with the selective estrogen receptor down-regulator [SERD] fulvestrant (Faslodex) was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo, reported Noah S. Kornblum, MD, of Montefiore Einstein Center for Cancer Care, New York.

This study provides additional evidence that adding everolimus to anti-estrogen therapy in AI-resistant disease improves clinical outcomes,” he said at the San Antonio Breast Cancer Symposium.

Kornblum_Noah_NY_web.jpg

Potential role for the combination?

Following the presentation, SABCS fixture Steven “Vogl, New York” Vogl, MD, asked what to do when fulvestrant-based therapy fails.*

“I’m interested in what to do after progression. Let’s say the patient gets fulvestrant, gets everolimus, has a nice response – 9 months later, the tumor gets worse. We’re all pretty sure we shouldn’t continue the fulvestrant. I would love PrECOG to do a study in those patients of giving megestrol or megestrol/everolimus, and see if the everolimus extended beyond progression does the patient some good, as does trastuzumab,” he said.

“Sounds like a good idea. I’m game, let’s roll up our sleeves and do it together,” Dr. Kornblum replied.

The study was sponsored by PrECOG with financial support from Novartis. Dr. Kornblum reported having no conflicts of interest.

Correction 12/8/16: An earlier version of this article misstated Dr. Steven Vogl's name.

SAN ANTONIO – Adding everolimus to fulvestrant doubled median progression-free survival among postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer resistant to therapy with an aromatase inhibitor [AI] in the PrECOG 0102 study.

In the randomized phase II trial, the combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) with the selective estrogen receptor down-regulator [SERD] fulvestrant (Faslodex) was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo, reported Noah S. Kornblum, MD, of Montefiore Einstein Center for Cancer Care, New York.

This study provides additional evidence that adding everolimus to anti-estrogen therapy in AI-resistant disease improves clinical outcomes,” he said at the San Antonio Breast Cancer Symposium.

Kornblum_Noah_NY_web.jpg

Potential role for the combination?

Following the presentation, SABCS fixture Steven “Vogl, New York” Vogl, MD, asked what to do when fulvestrant-based therapy fails.*

“I’m interested in what to do after progression. Let’s say the patient gets fulvestrant, gets everolimus, has a nice response – 9 months later, the tumor gets worse. We’re all pretty sure we shouldn’t continue the fulvestrant. I would love PrECOG to do a study in those patients of giving megestrol or megestrol/everolimus, and see if the everolimus extended beyond progression does the patient some good, as does trastuzumab,” he said.

“Sounds like a good idea. I’m game, let’s roll up our sleeves and do it together,” Dr. Kornblum replied.

The study was sponsored by PrECOG with financial support from Novartis. Dr. Kornblum reported having no conflicts of interest.

Correction 12/8/16: An earlier version of this article misstated Dr. Steven Vogl's name.

SAN ANTONIO – Adding everolimus to fulvestrant doubled median progression-free survival among postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer resistant to therapy with an aromatase inhibitor [AI] in the PrECOG 0102 study.

In the randomized phase II trial, the combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) with the selective estrogen receptor down-regulator [SERD] fulvestrant (Faslodex) was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo, reported Noah S. Kornblum, MD, of Montefiore Einstein Center for Cancer Care, New York.

This study provides additional evidence that adding everolimus to anti-estrogen therapy in AI-resistant disease improves clinical outcomes,” he said at the San Antonio Breast Cancer Symposium.

Kornblum_Noah_NY_web.jpg

Potential role for the combination?

Following the presentation, SABCS fixture Steven “Vogl, New York” Vogl, MD, asked what to do when fulvestrant-based therapy fails.*

“I’m interested in what to do after progression. Let’s say the patient gets fulvestrant, gets everolimus, has a nice response – 9 months later, the tumor gets worse. We’re all pretty sure we shouldn’t continue the fulvestrant. I would love PrECOG to do a study in those patients of giving megestrol or megestrol/everolimus, and see if the everolimus extended beyond progression does the patient some good, as does trastuzumab,” he said.

“Sounds like a good idea. I’m game, let’s roll up our sleeves and do it together,” Dr. Kornblum replied.

The study was sponsored by PrECOG with financial support from Novartis. Dr. Kornblum reported having no conflicts of interest.

Correction 12/8/16: An earlier version of this article misstated Dr. Steven Vogl's name.

SAN ANTONIO – Most women with hormone receptor–positive breast cancer treated with an aromatase inhibitor will eventually develop resistance to these agents. Strategies for overcoming resistance include the addition of everolimus (Affinitor) to a steroidal aromatase inhibitor (AI) such as exemestane (Aromasin), as in the BOLERO-2 trial.

Alternatively, blocking estrogen-receptor signaling through the use of a selective estrogen receptor down regulator, such as fulvestrant (Faslodex), may result in more complete blockade of the ER signaling pathway than would a steroidal AI such as exemestane.

In this video interview at the San Antonio Breast Cancer Symposium, Noah S. Kornblum, MD, of the Montefiore-Einstein Center for Cancer Care, New York, discusses findings from the phase II PrECOG 0102 trial comparing a combination of fulvestrant and everolimus to fulvestrant and placebo for the treatment of postmenopausal women with hormone receptor–positive, HER2-negative breast cancer resistant to AI therapy.

The combination was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo (hazard ratio, 0.60; P = .02).

Dr. Kornblum says that the study provides additional evidence for adding everolimus to anti-estrogen therapy in AI-resistant disease.

SAN ANTONIO – Most women with hormone receptor–positive breast cancer treated with an aromatase inhibitor will eventually develop resistance to these agents. Strategies for overcoming resistance include the addition of everolimus (Affinitor) to a steroidal aromatase inhibitor (AI) such as exemestane (Aromasin), as in the BOLERO-2 trial.

Alternatively, blocking estrogen-receptor signaling through the use of a selective estrogen receptor down regulator, such as fulvestrant (Faslodex), may result in more complete blockade of the ER signaling pathway than would a steroidal AI such as exemestane.

In this video interview at the San Antonio Breast Cancer Symposium, Noah S. Kornblum, MD, of the Montefiore-Einstein Center for Cancer Care, New York, discusses findings from the phase II PrECOG 0102 trial comparing a combination of fulvestrant and everolimus to fulvestrant and placebo for the treatment of postmenopausal women with hormone receptor–positive, HER2-negative breast cancer resistant to AI therapy.

The combination was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo (hazard ratio, 0.60; P = .02).

Dr. Kornblum says that the study provides additional evidence for adding everolimus to anti-estrogen therapy in AI-resistant disease.

SAN ANTONIO – Most women with hormone receptor–positive breast cancer treated with an aromatase inhibitor will eventually develop resistance to these agents. Strategies for overcoming resistance include the addition of everolimus (Affinitor) to a steroidal aromatase inhibitor (AI) such as exemestane (Aromasin), as in the BOLERO-2 trial.

Alternatively, blocking estrogen-receptor signaling through the use of a selective estrogen receptor down regulator, such as fulvestrant (Faslodex), may result in more complete blockade of the ER signaling pathway than would a steroidal AI such as exemestane.

In this video interview at the San Antonio Breast Cancer Symposium, Noah S. Kornblum, MD, of the Montefiore-Einstein Center for Cancer Care, New York, discusses findings from the phase II PrECOG 0102 trial comparing a combination of fulvestrant and everolimus to fulvestrant and placebo for the treatment of postmenopausal women with hormone receptor–positive, HER2-negative breast cancer resistant to AI therapy.

The combination was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo (hazard ratio, 0.60; P = .02).

Dr. Kornblum says that the study provides additional evidence for adding everolimus to anti-estrogen therapy in AI-resistant disease.

SAN DIEGO – It took a clinical trial with a byzantine design to prove it, but neither posttransplant consolidation therapy nor second transplant offered any additional survival benefits to patients with multiple myeloma, including patients with high-risk disease who were treated with an upfront thalidomide analogue and a proteasome inhibitor, followed by stem cell transplant and lenalidomide maintenance.

Among 758 patients with multiple myeloma who underwent standard induction therapy, followed by melphalan conditioning and autologous stem cell transplant (ASCT), there were no differences in either progression-free survival (PFS) or overall survival (OS) among patients assigned to follow-on therapy with either lenalidomide (Revlimid) maintenance alone; consolidation therapy with four cycles of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD), followed by lenalidomide maintenance; or second transplant, followed by lenalidomide maintenance, reported  Edward A. Stadtmauer, MD, coleader of the hematologic malignancies program at the Abramson Cancer Center, and chief of the section of hematologic malignancies, University of Pennsylvania, Philadelphia.

122294_Stadtmauer_Edward_A_web.jpg

SAN DIEGO – It took a clinical trial with a byzantine design to prove it, but neither posttransplant consolidation therapy nor second transplant offered any additional survival benefits to patients with multiple myeloma, including patients with high-risk disease who were treated with an upfront thalidomide analogue and a proteasome inhibitor, followed by stem cell transplant and lenalidomide maintenance.

Among 758 patients with multiple myeloma who underwent standard induction therapy, followed by melphalan conditioning and autologous stem cell transplant (ASCT), there were no differences in either progression-free survival (PFS) or overall survival (OS) among patients assigned to follow-on therapy with either lenalidomide (Revlimid) maintenance alone; consolidation therapy with four cycles of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD), followed by lenalidomide maintenance; or second transplant, followed by lenalidomide maintenance, reported  Edward A. Stadtmauer, MD, coleader of the hematologic malignancies program at the Abramson Cancer Center, and chief of the section of hematologic malignancies, University of Pennsylvania, Philadelphia.

122294_Stadtmauer_Edward_A_web.jpg

SAN DIEGO – It took a clinical trial with a byzantine design to prove it, but neither posttransplant consolidation therapy nor second transplant offered any additional survival benefits to patients with multiple myeloma, including patients with high-risk disease who were treated with an upfront thalidomide analogue and a proteasome inhibitor, followed by stem cell transplant and lenalidomide maintenance.

Among 758 patients with multiple myeloma who underwent standard induction therapy, followed by melphalan conditioning and autologous stem cell transplant (ASCT), there were no differences in either progression-free survival (PFS) or overall survival (OS) among patients assigned to follow-on therapy with either lenalidomide (Revlimid) maintenance alone; consolidation therapy with four cycles of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD), followed by lenalidomide maintenance; or second transplant, followed by lenalidomide maintenance, reported  Edward A. Stadtmauer, MD, coleader of the hematologic malignancies program at the Abramson Cancer Center, and chief of the section of hematologic malignancies, University of Pennsylvania, Philadelphia.

122294_Stadtmauer_Edward_A_web.jpg

SAN DIEGO – For patients with indolent non-Hodgkin lymphoma, adding the anti-CD20 antibody rituximab to a standard-combination chemotherapy regimen resulted in significant improvements in survival, compared with chemotherapy alone. Obinutuzumab (Gazyva), a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, is being explored in various combinations for the treatment of indolent lymphomas, including follicular lymphoma and marginal zone lymphoma.

In this video interview from the annual meeting of the American Society of Hematology, Robert Marcus, FRCP, of King’s College Hospital, London, discussed results of the phase III GALLIUM study, in which patients with untreated follicular lymphoma were randomly assigned to one of three chemotherapy regimens with either obinutuzumab or rituximab. The primary endpoint of investigator-assessed 3-year progression-free survival (PFS) at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio (HR) favoring obinutuzumab of 0.68 (P = .0012).

Respective 3-year overall survival rates at 3 years were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

The GALLIUM trial is sponsored by F. Hoffmann-La Roche. Dr. Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – For patients with indolent non-Hodgkin lymphoma, adding the anti-CD20 antibody rituximab to a standard-combination chemotherapy regimen resulted in significant improvements in survival, compared with chemotherapy alone. Obinutuzumab (Gazyva), a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, is being explored in various combinations for the treatment of indolent lymphomas, including follicular lymphoma and marginal zone lymphoma.

In this video interview from the annual meeting of the American Society of Hematology, Robert Marcus, FRCP, of King’s College Hospital, London, discussed results of the phase III GALLIUM study, in which patients with untreated follicular lymphoma were randomly assigned to one of three chemotherapy regimens with either obinutuzumab or rituximab. The primary endpoint of investigator-assessed 3-year progression-free survival (PFS) at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio (HR) favoring obinutuzumab of 0.68 (P = .0012).

Respective 3-year overall survival rates at 3 years were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

The GALLIUM trial is sponsored by F. Hoffmann-La Roche. Dr. Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – For patients with indolent non-Hodgkin lymphoma, adding the anti-CD20 antibody rituximab to a standard-combination chemotherapy regimen resulted in significant improvements in survival, compared with chemotherapy alone. Obinutuzumab (Gazyva), a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, is being explored in various combinations for the treatment of indolent lymphomas, including follicular lymphoma and marginal zone lymphoma.

In this video interview from the annual meeting of the American Society of Hematology, Robert Marcus, FRCP, of King’s College Hospital, London, discussed results of the phase III GALLIUM study, in which patients with untreated follicular lymphoma were randomly assigned to one of three chemotherapy regimens with either obinutuzumab or rituximab. The primary endpoint of investigator-assessed 3-year progression-free survival (PFS) at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio (HR) favoring obinutuzumab of 0.68 (P = .0012).

Respective 3-year overall survival rates at 3 years were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

The GALLIUM trial is sponsored by F. Hoffmann-La Roche. Dr. Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – Obinutuzumab, a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, offered a progression-free survival (PFS) edge over rituximab when combined with standard chemotherapy in patients with previously untreated advanced follicular lymphoma.

Marcus_Robert_NY_web.JPG

attended the presentation of the GALLIUM data at a plenary session during the American Society of Hematology annual meeting indicated that despite the data, they weren’t ready to make a switch to the newer, costlier antibody.

“I feel that it is not convincing for practice-changing,” said Kanti R. Rai, MD, professor of medicine and molecular medicine at Hofstra University, Hempstead, N.Y.

“Unless we have evidence of a survival advantage in indolent disease, progression-free survivorship is not an adequate reason to jump to another antibody,” he said in an interview.

In GALLIUM, the primary endpoint of investigator-assessed 3-year PFS at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio of 0.68 favoring obinutuzumab (P = .0012).

Respective 3-year overall survival rates were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

Indolent lymphoma trial

The GALLIUM trial is a phase III study comparing obinutuzumab with rituximab when paired with one of three standard chemotherapy regimens for indolent non-Hodgkin lymphomas, including follicular lymphoma and splenic, nodal, or extranodal marginal zone lymphoma. Dr. Marcus presented data on patients with follicular lymphoma only.

The antibodies were delivered in combination with either CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone; 33.1% of patients), CVP (cyclophosphamide, vincristine, prednisone; 9.8%) or bendamustine alone (B; 57.1%) as the chemotherapy backbone. The choice of regimen was at the discretion of the treating center.

A total of 1,202 patients with follicular lymphoma were enrolled and randomized to treatment and were included in an intention-to-treat analysis.

The treatment arms were well balanced with regard to distribution of patients characteristics, with approximately 21% in each arm having Follicular Lymphoma International Prognostic Index low-risk disease; 37% having intermediate-risk disease; and 34% having high-risk disease.

Roughly half of patients in each arm had bone marrow involvement, and two-thirds had extranodal involvement.

Obinutuzumab was dosed 1,000 mg IV on days 1, 8, and 15 of cycle one, and either on day 1 of cycles two through eight every 3 weeks, or every 4 weeks during cycles two through six.

Overall response rates at the end of induction were 86.9% with rituximab and 88.5% with obinutuzumab, with complete responses of 23.8% and 19.5%, respectively.

As noted before, investigator-assessed PFS favored obinutuzumab, as did PFS assessed by independent reviewer, at 81.9% vs. 77.9% for rituximab (HR, 0.71; P = .0138).

The newer antibody also had a slight edge in time to new treatment, with 87.1% of patients on obinutuzumab not starting on new therapy, compared with 81.2% of patients on rituximab.

More bendamustine deaths

Nearly all patients in each arm had an adverse event, with grade 3 or greater events occurring in 74.6% of patients on obinutuzumab vs. 67.8% on rituximab. Rates of neutropenia, leukopenia, febrile neutropenia, infusion reactions, and thrombocytopenia were all slightly higher with obinutuzumab. Grade 3 or greater infections occurred in 20% with obinutuzumab, compared with 15.6% with rituximab.

“What we did note, however, was a high level of mortality in patients receiving either obinutuzumab-based therapy or rituximab-based therapy, which were no different between the two arms and were somewhat higher than one might expect from patients receiving induction treatment in follicular lymphoma. Hence, we did a more detailed analysis of safety by treatment regimen,” Dr. Marcus said.

There were more deaths among patients treated with bendamustine (5.6% for patients in the B-obinutuzumab cohort, and 4.4% of patients in the B-rituximab cohort) vs. 1.6% and 2.0%, respectively, for patients on CHOP, and 1.6 and 1.8% for patients on CVP.

Dose effect?

John P. Leonard, MD, from Cornell University, New York , who introduced Dr. Marcus, commented that PFS may not be the ideal endpoint for patients with follicular lymphoma.

Leonard_John_P_NY_web.jpg

He pointed out that in trials comparing rituximab with obinutuzumab for other diseases, results have been mixed, with obinutuzumab showing superiority in chronic lymphocytic leukemia, but in data presented elsewhere at ASH 2016, obinutuzumab was not superior to rituximab for treatment of diffuse large B-cell lymphoma.

“One question is whether obinutuzumab, which is generally administered at a higher mg dose to patients, is in fact a better antibody or if it is in fact a dose effect,” he said.

In response to a similar question following his presentation, Dr. Marcus replied that, despite sharing a target, the two antibodies are different, with different mechanisms of action. He also noted that there is no evidence to suggest that rituximab potency would be greater in follicular lymphoma if it were given at higher doses.

The GALLIUM trial is sponsored by Hoffmann-La Roche, Dr, Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – Obinutuzumab, a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, offered a progression-free survival (PFS) edge over rituximab when combined with standard chemotherapy in patients with previously untreated advanced follicular lymphoma.

Marcus_Robert_NY_web.JPG

attended the presentation of the GALLIUM data at a plenary session during the American Society of Hematology annual meeting indicated that despite the data, they weren’t ready to make a switch to the newer, costlier antibody.

“I feel that it is not convincing for practice-changing,” said Kanti R. Rai, MD, professor of medicine and molecular medicine at Hofstra University, Hempstead, N.Y.

“Unless we have evidence of a survival advantage in indolent disease, progression-free survivorship is not an adequate reason to jump to another antibody,” he said in an interview.

In GALLIUM, the primary endpoint of investigator-assessed 3-year PFS at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio of 0.68 favoring obinutuzumab (P = .0012).

Respective 3-year overall survival rates were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

Indolent lymphoma trial

The GALLIUM trial is a phase III study comparing obinutuzumab with rituximab when paired with one of three standard chemotherapy regimens for indolent non-Hodgkin lymphomas, including follicular lymphoma and splenic, nodal, or extranodal marginal zone lymphoma. Dr. Marcus presented data on patients with follicular lymphoma only.

The antibodies were delivered in combination with either CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone; 33.1% of patients), CVP (cyclophosphamide, vincristine, prednisone; 9.8%) or bendamustine alone (B; 57.1%) as the chemotherapy backbone. The choice of regimen was at the discretion of the treating center.

A total of 1,202 patients with follicular lymphoma were enrolled and randomized to treatment and were included in an intention-to-treat analysis.

The treatment arms were well balanced with regard to distribution of patients characteristics, with approximately 21% in each arm having Follicular Lymphoma International Prognostic Index low-risk disease; 37% having intermediate-risk disease; and 34% having high-risk disease.

Roughly half of patients in each arm had bone marrow involvement, and two-thirds had extranodal involvement.

Obinutuzumab was dosed 1,000 mg IV on days 1, 8, and 15 of cycle one, and either on day 1 of cycles two through eight every 3 weeks, or every 4 weeks during cycles two through six.

Overall response rates at the end of induction were 86.9% with rituximab and 88.5% with obinutuzumab, with complete responses of 23.8% and 19.5%, respectively.

As noted before, investigator-assessed PFS favored obinutuzumab, as did PFS assessed by independent reviewer, at 81.9% vs. 77.9% for rituximab (HR, 0.71; P = .0138).

The newer antibody also had a slight edge in time to new treatment, with 87.1% of patients on obinutuzumab not starting on new therapy, compared with 81.2% of patients on rituximab.

More bendamustine deaths

Nearly all patients in each arm had an adverse event, with grade 3 or greater events occurring in 74.6% of patients on obinutuzumab vs. 67.8% on rituximab. Rates of neutropenia, leukopenia, febrile neutropenia, infusion reactions, and thrombocytopenia were all slightly higher with obinutuzumab. Grade 3 or greater infections occurred in 20% with obinutuzumab, compared with 15.6% with rituximab.

“What we did note, however, was a high level of mortality in patients receiving either obinutuzumab-based therapy or rituximab-based therapy, which were no different between the two arms and were somewhat higher than one might expect from patients receiving induction treatment in follicular lymphoma. Hence, we did a more detailed analysis of safety by treatment regimen,” Dr. Marcus said.

There were more deaths among patients treated with bendamustine (5.6% for patients in the B-obinutuzumab cohort, and 4.4% of patients in the B-rituximab cohort) vs. 1.6% and 2.0%, respectively, for patients on CHOP, and 1.6 and 1.8% for patients on CVP.

Dose effect?

John P. Leonard, MD, from Cornell University, New York , who introduced Dr. Marcus, commented that PFS may not be the ideal endpoint for patients with follicular lymphoma.

Leonard_John_P_NY_web.jpg

He pointed out that in trials comparing rituximab with obinutuzumab for other diseases, results have been mixed, with obinutuzumab showing superiority in chronic lymphocytic leukemia, but in data presented elsewhere at ASH 2016, obinutuzumab was not superior to rituximab for treatment of diffuse large B-cell lymphoma.

“One question is whether obinutuzumab, which is generally administered at a higher mg dose to patients, is in fact a better antibody or if it is in fact a dose effect,” he said.

In response to a similar question following his presentation, Dr. Marcus replied that, despite sharing a target, the two antibodies are different, with different mechanisms of action. He also noted that there is no evidence to suggest that rituximab potency would be greater in follicular lymphoma if it were given at higher doses.

The GALLIUM trial is sponsored by Hoffmann-La Roche, Dr, Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – Obinutuzumab, a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, offered a progression-free survival (PFS) edge over rituximab when combined with standard chemotherapy in patients with previously untreated advanced follicular lymphoma.

Marcus_Robert_NY_web.JPG

attended the presentation of the GALLIUM data at a plenary session during the American Society of Hematology annual meeting indicated that despite the data, they weren’t ready to make a switch to the newer, costlier antibody.

“I feel that it is not convincing for practice-changing,” said Kanti R. Rai, MD, professor of medicine and molecular medicine at Hofstra University, Hempstead, N.Y.

“Unless we have evidence of a survival advantage in indolent disease, progression-free survivorship is not an adequate reason to jump to another antibody,” he said in an interview.

In GALLIUM, the primary endpoint of investigator-assessed 3-year PFS at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio of 0.68 favoring obinutuzumab (P = .0012).

Respective 3-year overall survival rates were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

Indolent lymphoma trial

The GALLIUM trial is a phase III study comparing obinutuzumab with rituximab when paired with one of three standard chemotherapy regimens for indolent non-Hodgkin lymphomas, including follicular lymphoma and splenic, nodal, or extranodal marginal zone lymphoma. Dr. Marcus presented data on patients with follicular lymphoma only.

The antibodies were delivered in combination with either CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone; 33.1% of patients), CVP (cyclophosphamide, vincristine, prednisone; 9.8%) or bendamustine alone (B; 57.1%) as the chemotherapy backbone. The choice of regimen was at the discretion of the treating center.

A total of 1,202 patients with follicular lymphoma were enrolled and randomized to treatment and were included in an intention-to-treat analysis.

The treatment arms were well balanced with regard to distribution of patients characteristics, with approximately 21% in each arm having Follicular Lymphoma International Prognostic Index low-risk disease; 37% having intermediate-risk disease; and 34% having high-risk disease.

Roughly half of patients in each arm had bone marrow involvement, and two-thirds had extranodal involvement.

Obinutuzumab was dosed 1,000 mg IV on days 1, 8, and 15 of cycle one, and either on day 1 of cycles two through eight every 3 weeks, or every 4 weeks during cycles two through six.

Overall response rates at the end of induction were 86.9% with rituximab and 88.5% with obinutuzumab, with complete responses of 23.8% and 19.5%, respectively.

As noted before, investigator-assessed PFS favored obinutuzumab, as did PFS assessed by independent reviewer, at 81.9% vs. 77.9% for rituximab (HR, 0.71; P = .0138).

The newer antibody also had a slight edge in time to new treatment, with 87.1% of patients on obinutuzumab not starting on new therapy, compared with 81.2% of patients on rituximab.

More bendamustine deaths

Nearly all patients in each arm had an adverse event, with grade 3 or greater events occurring in 74.6% of patients on obinutuzumab vs. 67.8% on rituximab. Rates of neutropenia, leukopenia, febrile neutropenia, infusion reactions, and thrombocytopenia were all slightly higher with obinutuzumab. Grade 3 or greater infections occurred in 20% with obinutuzumab, compared with 15.6% with rituximab.

“What we did note, however, was a high level of mortality in patients receiving either obinutuzumab-based therapy or rituximab-based therapy, which were no different between the two arms and were somewhat higher than one might expect from patients receiving induction treatment in follicular lymphoma. Hence, we did a more detailed analysis of safety by treatment regimen,” Dr. Marcus said.

There were more deaths among patients treated with bendamustine (5.6% for patients in the B-obinutuzumab cohort, and 4.4% of patients in the B-rituximab cohort) vs. 1.6% and 2.0%, respectively, for patients on CHOP, and 1.6 and 1.8% for patients on CVP.

Dose effect?

John P. Leonard, MD, from Cornell University, New York , who introduced Dr. Marcus, commented that PFS may not be the ideal endpoint for patients with follicular lymphoma.

Leonard_John_P_NY_web.jpg

He pointed out that in trials comparing rituximab with obinutuzumab for other diseases, results have been mixed, with obinutuzumab showing superiority in chronic lymphocytic leukemia, but in data presented elsewhere at ASH 2016, obinutuzumab was not superior to rituximab for treatment of diffuse large B-cell lymphoma.

“One question is whether obinutuzumab, which is generally administered at a higher mg dose to patients, is in fact a better antibody or if it is in fact a dose effect,” he said.

In response to a similar question following his presentation, Dr. Marcus replied that, despite sharing a target, the two antibodies are different, with different mechanisms of action. He also noted that there is no evidence to suggest that rituximab potency would be greater in follicular lymphoma if it were given at higher doses.

The GALLIUM trial is sponsored by Hoffmann-La Roche, Dr, Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – A new multi-arm clinical trial aims to transform the treatment of de novo acute myeloid leukemia, a deadly blood cancer whose standard of care has remained essentially stagnant for 40 years.

Launched in October 2016, the multicenter BEAT AML Master Trial provides genomic results of bone marrow biopsies in just 7 days, according to Brian J. Druker, MD, director of the Knight Cancer Institute at Oregon Health and Science University, Portland. With results that fast, patients can quickly receive whichever therapy targets the mutation shared by most or all their leukemia cells, Dr. Druker and other researchers said at a press briefing at the annual meeting of the American Society of Hematology.

Patients who lack targetable markers will be offered investigational therapies that have shown broad activity in AML, the researchers said. The goal is for all participants to receive optimized treatment – whether or not that leads to an FDA approval, they emphasized.

Centers now participating in this trial include Memorial Sloan Kettering, Ohio State University, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Oregon Health and Science University. More centers will join soon, according to the Leukemia & Lymphoma Society, which is sponsoring the trial. Researchers designed the trial with input from the FDA and pharmaceutical companies, they said.

In a video interview, Dr. Druker discussed key aspects of the trial and how it could advance treatment options for AML. Dr. Druker, whose work on imatinib helped pioneer precision medicine in cancer, disclosed ties to a number of pharmaceutical companies.

SAN DIEGO – A new multi-arm clinical trial aims to transform the treatment of de novo acute myeloid leukemia, a deadly blood cancer whose standard of care has remained essentially stagnant for 40 years.

Launched in October 2016, the multicenter BEAT AML Master Trial provides genomic results of bone marrow biopsies in just 7 days, according to Brian J. Druker, MD, director of the Knight Cancer Institute at Oregon Health and Science University, Portland. With results that fast, patients can quickly receive whichever therapy targets the mutation shared by most or all their leukemia cells, Dr. Druker and other researchers said at a press briefing at the annual meeting of the American Society of Hematology.

Patients who lack targetable markers will be offered investigational therapies that have shown broad activity in AML, the researchers said. The goal is for all participants to receive optimized treatment – whether or not that leads to an FDA approval, they emphasized.

Centers now participating in this trial include Memorial Sloan Kettering, Ohio State University, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Oregon Health and Science University. More centers will join soon, according to the Leukemia & Lymphoma Society, which is sponsoring the trial. Researchers designed the trial with input from the FDA and pharmaceutical companies, they said.

In a video interview, Dr. Druker discussed key aspects of the trial and how it could advance treatment options for AML. Dr. Druker, whose work on imatinib helped pioneer precision medicine in cancer, disclosed ties to a number of pharmaceutical companies.

SAN DIEGO – A new multi-arm clinical trial aims to transform the treatment of de novo acute myeloid leukemia, a deadly blood cancer whose standard of care has remained essentially stagnant for 40 years.

Launched in October 2016, the multicenter BEAT AML Master Trial provides genomic results of bone marrow biopsies in just 7 days, according to Brian J. Druker, MD, director of the Knight Cancer Institute at Oregon Health and Science University, Portland. With results that fast, patients can quickly receive whichever therapy targets the mutation shared by most or all their leukemia cells, Dr. Druker and other researchers said at a press briefing at the annual meeting of the American Society of Hematology.

Patients who lack targetable markers will be offered investigational therapies that have shown broad activity in AML, the researchers said. The goal is for all participants to receive optimized treatment – whether or not that leads to an FDA approval, they emphasized.

Centers now participating in this trial include Memorial Sloan Kettering, Ohio State University, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Oregon Health and Science University. More centers will join soon, according to the Leukemia & Lymphoma Society, which is sponsoring the trial. Researchers designed the trial with input from the FDA and pharmaceutical companies, they said.

In a video interview, Dr. Druker discussed key aspects of the trial and how it could advance treatment options for AML. Dr. Druker, whose work on imatinib helped pioneer precision medicine in cancer, disclosed ties to a number of pharmaceutical companies.