Dr. Flaherty on the Rationale to Explore Triplet Therapy in BRAF V600E-Mutant Melanoma

Keith T. Flaherty, MD, director, Henri and Belinda Termeer Center for Targeted Therapy and director of clinical research, Massachusetts General Hospital Cancer Center, and professor of medicine, Harvard Medical School, discusses the rationale to explore triplet therapy in BRAF V600-mutant melanoma.

Flaherty presented the updated results of the phase III COLUMBUS trial of encorafenib (Braftovi) plus binimetinib (Mektovi) versus vemurafenib (Zelboraf) or encorafenib in patients with BRAF V600-mutant melanoma at the 2019 ASCO Annual Meeting. Although the combination performed better than either agent alone, researchers are looking to extend benefit of combined BRAF/MEK inhibition by adding another therapy to the regimen, explains Flaherty. At 4 years of follow-up, approximately 30% of a subset of patients remain progression-free. However, the majority do not respond or will lose their response to the combination.

One triplet that is believed to induce higher response rates is the combination of a BRAF, MEK, and PD-1 antibody, says Flaherty. Several studies have investigated these combinations, and 2 randomized trials have already been completed.