Dr. Flaherty Discusses BRAF Inhibitors in Melanoma

Keith T. Flaherty, MD, director, Termeer Center for Targeted Therapy, Massachusetts General Hospital Cancer Center, professor of medicine, Harvard Medical School, discusses BRAF inhibitors for the treatment of patients with melanoma.

It is well-established that mutated BRAF is a therapeutic target in melanoma, with about 45% of patients with advanced melanoma having activating mutations in BRAF, Flaherty says. Vemurafenib (Zelboraf) and dabrafenib (Mekinist) were the first agents to prove that BRAF was an important therapeutic target. It was then discovered that reactivation of the MEK pathway was a common theme, and there were available MEK inhibitors in development targeting the downstream component in the pathway from BRAF. Flaherty says that it was then conceived that combining BRAF and MEK inhibitors together could be an approach, and it was subsequently validated 2 times over.

The most recent BRAF plus MEK combination is encorafenib (Braftovi) with binimetinib (Mektovi). This combination achieved FDA approval in June 2018 for the treatment of patients with BRAF-mutant unresectable or metastatic melanoma, based on findings from the phase III COLUMBUS trial.