First Drug Combination Approved for Unresectable or Metastatic Melanoma

Jayson Slotnik, JD, MPH

February 2014, Vol 5, No 1 - FDA Approvals, News & Updates


The US Food and Drug Admin­istration (FDA) approved the use of dabrafenib (Tafinlar; GlaxoSmith­Kline) plus trametinib (Mekinist; GlaxoSmithKline) as a new combination therapy for the treatment of patients with advanced melanoma that is unresectable or metastatic. The 2 drugs were individually approved by the FDA in 2013 for melanoma. Each of the 2 drugs blocks molecular signaling in different sites of the same pathway that promotes cancer-cell growth. Dabrafenib was initially approved for patients with melanoma whose tumors express the BRAF V600E mutation. The dabrafenib-trametinib combination is indicated for patients with melanoma who also have the BRAF V600E or BRAF V600K mutation. Approximately 50% of skin melanomas have a BRAF mutation. 

“Mekinist and Tafinlar are the first drugs approved for combination treatment of melanoma,” said Richard Pazdur, MD, Director of the FDA’s Office of Hematology and Oncology Products. This approval illustrates the value of continuing to study drugs in combination for clinical development.”

The FDA approval was based on results of a clinical trial of 162 patients with unresectable or metastatic melanoma with the BRAF V600E or BRAF V600K mutation; the majority of the patients were treatment-naïve. They received dabrafenib as a single agent until their disease progressed or their side effects became intolerable, at which point they began using the combination. Overall, 76% of patients receiving the combination had an objective response for an average of 10.5 months compared with 54% of patients receiving dabrafenib alone who had an objective response lasting 5.6 months. Clinical trials are ongoing to determine whether this combination will also result in improved survival.

The side effects reported with the combination are similar to those reported with each individual drug. Specifically, the combination was associated with an increase in the incidence and severity of fever.

The FDA approved this combination under its accelerated program, and also reviewed it under its priority review. (January 8, 2014)