BRAF/MEK Combination Highly Effective in Melanoma

Source: OncLive, November 2015

Adding the MEK inhibitor trametinib (Mekinist) to the BRAF inhibitor dabrafenib (Tafinlar) significantly improves long-term outcomes while lowering certain adverse events (AEs) associated with either agent alone for patients with BRAF-mutated metastatic melanoma, according to a talk by Jeffrey Weber, MD, PhD, at the 2015 Chemotherapy Foundation Symposium.

“The median survival for dabrafenib/trametinib is a very impressive 25 months, and you can’t get much better than that in melanoma. One-year survival is 74%—very impressive," said Weber, from the NYU Langone Medical Center’s Laura and Isaac Perlmutter Cancer Center. “This is one of the few times in oncology that adding a second drug to one drug actually decreases the side effects."

In 2002, BRAF mutations were discovered and found to be present in many malignancies. Following this discovery, BRAF inhibitors were quickly developed for patients with melanoma, with vemurafenib (Zelboraf) approved in 2011 followed in 2013 by dabrafenib and trametinib. Additionally, in January 2014, the combination of dabrafenib and trametinib received an accelerated approval for patients with BRAF-mutant metastatic melanoma.

“BRAF was felt to be a driver gene because tumor growth became dependent upon it if mutated, and if it were knocked out they would not grow and display all of the features of invasive cancer," Weber explained. “Much effort went into developing specific BRAF inhibitors as anticancer agents, and two have been FDA approved, as has a MEK inhibitor, so far."

Two phase III studies assessed the combination of dabrafenib and trametinib for patients with BRAF-positive melanoma, to support a full approval for the combination. The FDA is currently evaluating data from these studies, with a decision expected in the next few weeks………..