MAPK inhibitor combo offers prolonged survival from BRAF+ advanced melanoma

Combination therapy to inhibit the MAP kinase pathway is associated with a median overall survival of more than 2 years for patients with metastatic melanoma positive for the BRAF V600 mutation who have not previously received a BRAF inhibitor.

An analysis of data from a phase I and II trial of the BRAF inhibitor dabrafenib (Tafinlar), 150 mg twice daily, and the MEK inhibitor trametinib (Mekinist), 2 mg once daily, in 78 BRAF inhibitor–naïve patients with metastatic melanoma showed that in a non-randomized cohort (part B) the median overall survival (OS) was 27.4 months. In a cohort randomized to the same doses (part C), the median OS was 25 months, reported Dr. Georgina V. Long and her colleagues from the Melanoma Institute Australia and the University of Sydney in the Journal of Clinical Oncology.

Among 24 patients treated in part B, progression-free survival (PFS) was 18% at 3 years.

“The combination has an acceptable long-term safety profile and is a standard of care for patients with BRAF mutation–positive metastatic melanoma, particularly given the recent publications demonstrating a significant improvement in the PFS and OS in phase III trials of combination versus single-agent BRAF inhibitors,” the investigators wrote (J Clin Oncol. 2016 Jan 25. doi: 10.1200/JCO.2015.62.9345).

The investigators conducted the analysis to determine which patients were the most likely to benefit from combination therapy of the MAP (mitogen-active protein) kinase pathway.

They observed that in the part B, non-randomized cohort, OS was 72% at 1 year, 60% at 2 tears, and 47% at 3 years. In the part C, randomized cohort, OS was 80%, 51%, and 38%, respectively.

Factors associated with better OS in Cox proportional hazards regression models included metastases to fewer than three organs sites, and lower levels of lactate dehydrogenase (LDH) at baseline. Not surprisingly, a complete response to therapy was also associated with better survival. Three-year OS rates were 62% for patients with normal baseline LDH levels, and 63% for patients who had a complete response.

Combination therapy to inhibit the MAP kinase pathway is associated with a median overall survival of more than 2 years for patients with metastatic melanoma positive for the BRAF V600 mutation who have not previously received a BRAF inhibitor.

An analysis of data from a phase I and II trial of the BRAF inhibitor dabrafenib (Tafinlar), 150 mg twice daily, and the MEK inhibitor trametinib (Mekinist), 2 mg once daily, in 78 BRAF inhibitor–naïve patients with metastatic melanoma showed that in a non-randomized cohort (part B) the median overall survival (OS) was 27.4 months. In a cohort randomized to the same doses (part C), the median OS was 25 months, reported Dr. Georgina V. Long and her colleagues from the Melanoma Institute Australia and the University of Sydney in the Journal of Clinical Oncology.

Among 24 patients treated in part B, progression-free survival (PFS) was 18% at 3 years.

“The combination has an acceptable long-term safety profile and is a standard of care for patients with BRAF mutation–positive metastatic melanoma, particularly given the recent publications demonstrating a significant improvement in the PFS and OS in phase III trials of combination versus single-agent BRAF inhibitors,” the investigators wrote (J Clin Oncol. 2016 Jan 25. doi: 10.1200/JCO.2015.62.9345).

The investigators conducted the analysis to determine which patients were the most likely to benefit from combination therapy of the MAP (mitogen-active protein) kinase pathway.

They observed that in the part B, non-randomized cohort, OS was 72% at 1 year, 60% at 2 tears, and 47% at 3 years. In the part C, randomized cohort, OS was 80%, 51%, and 38%, respectively.

Factors associated with better OS in Cox proportional hazards regression models included metastases to fewer than three organs sites, and lower levels of lactate dehydrogenase (LDH) at baseline. Not surprisingly, a complete response to therapy was also associated with better survival. Three-year OS rates were 62% for patients with normal baseline LDH levels, and 63% for patients who had a complete response.

Combination therapy to inhibit the MAP kinase pathway is associated with a median overall survival of more than 2 years for patients with metastatic melanoma positive for the BRAF V600 mutation who have not previously received a BRAF inhibitor.

An analysis of data from a phase I and II trial of the BRAF inhibitor dabrafenib (Tafinlar), 150 mg twice daily, and the MEK inhibitor trametinib (Mekinist), 2 mg once daily, in 78 BRAF inhibitor–naïve patients with metastatic melanoma showed that in a non-randomized cohort (part B) the median overall survival (OS) was 27.4 months. In a cohort randomized to the same doses (part C), the median OS was 25 months, reported Dr. Georgina V. Long and her colleagues from the Melanoma Institute Australia and the University of Sydney in the Journal of Clinical Oncology.

Among 24 patients treated in part B, progression-free survival (PFS) was 18% at 3 years.

“The combination has an acceptable long-term safety profile and is a standard of care for patients with BRAF mutation–positive metastatic melanoma, particularly given the recent publications demonstrating a significant improvement in the PFS and OS in phase III trials of combination versus single-agent BRAF inhibitors,” the investigators wrote (J Clin Oncol. 2016 Jan 25. doi: 10.1200/JCO.2015.62.9345).

The investigators conducted the analysis to determine which patients were the most likely to benefit from combination therapy of the MAP (mitogen-active protein) kinase pathway.

They observed that in the part B, non-randomized cohort, OS was 72% at 1 year, 60% at 2 tears, and 47% at 3 years. In the part C, randomized cohort, OS was 80%, 51%, and 38%, respectively.

Factors associated with better OS in Cox proportional hazards regression models included metastases to fewer than three organs sites, and lower levels of lactate dehydrogenase (LDH) at baseline. Not surprisingly, a complete response to therapy was also associated with better survival. Three-year OS rates were 62% for patients with normal baseline LDH levels, and 63% for patients who had a complete response.