Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma

The combination of inhibitors to BRAF and MEK improved response rates and progression-free survival among patients with metastatic melanoma. Some toxicity was increased, but the incidence of second skin cancers was drastically reduced by the combination therapy. Approximately 50% of metastatic cutaneous melanomas harbor a BRAF V600 mutation, resulting in constitutive activation of the mitogen-activated protein kinase (MAPK) pathway. 1 , 2 These discoveries led to the development of agents that specifically target this driver mutation. The BRAF inhibitor vemurafenib (Zelboraf, Genentech) was approved worldwide on the basis of results from a phase 3 trial showing improved progression-free survival and overall survival, as compared with chemotherapy alone; the relative reduction in the risk of death was 63% and in the risk of disease progression was 74%. 3 Similar results were also reported for another BRAF inhibitor, dabrafenib, 4 which has also . . .