Cobimetinib, codeveloped by
Genentech and Exelixis, was approved in August 2015 in
Switzerland and November 2015 in the U.S. and Europe for the
treatment of unresectable or metastatic BRAFV600 mutationpositive
melanoma when used in combination with vemurafenib. Cobimetinib is a potent, highly selective reversible
inhibitor of mitogen-activated protein kinases (MEK) 1 and
2,120 which serves to inhibit phosphorylation of ERK1/2,121
disrupting the MAPK pathway which is responsible for cell
proliferation, cell survival, and migration.122 Combination of
cobimetinib with vemurafenib, an important BRAF inhibitor,123
enables targeting of multiple points on the MAPK pathway,
leading to overall enhanced tumor cell apoptosis and response
as compared to stand-alone treatment with vemurafenib.124
Specifically, in a representative trial of previously untreated
patients with BRAFV600 mutation-positive, unresectable, stage
IIIc or IV melanoma, combination of these two therapies led to
a significantly improved progression-free survival and overall
response rate versus patients treated only with vemurafenib.
