Vemurafenib and cobimetinib in BRAF-mutated melanoma

Vemurafenib interrupts the BRAF/MEK/ERK pathway in melanomas that harbour the BRAF V600E mutation (present in about 50% of patients). The addition of cobimetinib, a MEK inhibitor, to vemurafenib might prevent or delay the onset of resistance. In a previous open-label, phase 1b trial, 66 vemurafenib-refractory patients and 63 BRAF-inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma were treated with the combination vemurafanib and cobimetinib. In treatment-naive patients, median progression-free survival was 13·7 months, 87% of patients had an overall response, and 10% a complete response. An additional 10% of patients had stable disease.