Dr. Sullivan on Practice-Changing COMBI-d and COMBI-v Trials

Ryan J. Sullivan, MD, associate director, Melanoma Program, Massachusetts General Hospital Cancer Center, discusses the results of the COMBI-d and COMBI-v studies, led to changes in practice for patients with BRAF V600-mutant unresectable or metastatic melanoma.

Patients with the BRAF V600 mutation were first treated with the dabrafenib (Tafinlar) plus trametinib (Mekinist) combination in a clinical trial setting in 2010. Patients were able to take full doses and had “remarkable response rates,” according to Sullivan. A cohort of this phase I study found that these agents worked best in combination for this patient population, Sullivan explained.

The results from the phase I trial led to two phase III trials: COMBI-d and COMBI-v. COMBI-d examined dabrafenib plus trametinib versus dabrafenib plus placebo. COMBI-v compared dabrafenib with trametinib versus vemurafenib (Zelboraf) with placebo. Both trials showed higher response rates, progression-free survival, and overall survival with the dabrafenib plus trametinib combination, according to Sullivan. The combination was approved in 2014 to treat patients with BRAF V600-mutant unresectable or metastatic melanoma. These trials changed the standard of care for this patient population, added Sullivan.