Combination Regimen Options Under Investigation in Melanoma

Keith T. Flaherty, MD, a professor of medicine at Harvard Medical School, director of the Henri and Belinda Termeer Center for Targeted Therapy, and director of clinical research at Massachusetts General Hospital, discusses the combination regimens and the potential role for a 3-drug regimen as treatment for patients with melanoma. He says investigators have been searching for new combination strategies beyond the combination of BRAF and MEK inhibitors.

Not all patients respond to the BRAK/MEK combination, and for those patients that do respond, they can lose their response over time. A subpopulation of almost 30% remain progression free at 4-year follow-up and some patients even remained on therapy after disease progression, Flaherty notes. Overall, about 40% of patients were alive after 4 years, though some had progressed and found additional benefit from subsequent therapy..

This speaks to the need for improvement, Flaherty says. As patients continue to progress, there are other therapies available, including PD-1 inhibition. PD-1 inhibitors are the other primary consideration for these patients, but more therapies are still necessary.

The triplet combination of BRAF and MEK plus a PD-1 antibody is now being pursued in multiple studies. Two large randomized phase III trials will be coming out and the results are highly anticipated, Flaherty concludes.