The Food and Drug Administration has approved the once-daily oral MEK inhibitor cobimetinib in combination with vemurafenib to treat patients with advanced melanoma whose tumors express the BRAF V600E or V600K mutation.
“Today’s approval provides a new targeted treatment that, when added to vemurafenib, demonstrates greater benefit than vemurafenib alone in patients with BRAF mutation–positive melanoma,” said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a press release announcing the approval.
In a pivotal clinical trial, treatment-naive individuals with unresectable, locally advanced or metastatic melanoma whose tumors were positive for BRAF V600E or V600K mutations were randomized to receive the BRAF inhibitor vemurafenib plus placebo (n = 248) or to receive vemurafenib with cobimetinib (n = 247). At the time of data cut-off in May, 2014, median progression-free survival (PFS) was significantly longer for the cobimetinib group (9.9 vs. 6.2 months, hazard ratio, 0.51; P less than .001); PFS was the primary outcome measure.
Of the secondary outcome measures, objective response was seen in two of three patients on cobimetinib, compared with fewer than half of the placebo arm patients (68% vs. 45%; P less than .001). Another secondary outcome measure, overall survival, could not be calculated because too few events had occurred at the end of data collection.
More grade 3 or higher adverse events occurred for patients in the cobimetinib arm than the placebo arm (65% vs. 59%), but the difference was not statistically significant. Patients taking cobimetinib were no more likely than those taking placebo to discontinue taking the study drug.
Side effects most commonly associated with the combination of vemurafenib and cobimetinib included diarrhea, photosensitivity, nausea, fever, and vomiting.
Individuals taking both a BRAF inhibitor and a MEK inhibitor were less likely to develop nonmelanoma secondary skin cancers, a complication that affects about 25% of those taking vemurafenib alone.
Vemurafenib blocks BRAF, part of a molecular signaling pathway implicated in melanoma tumor cell growth and division. Cobimetinib can help delay tumor resistance to vemurafenib by targeting MEK, a gene in the same signaling pathway.
The senior investigator of the pivotal clinical trial, Dr. Antoni Ribas, said in a press release, “Today’s approval is a significant advance in the treatment of metastatic melanoma.
“For patients with a BRAF-mutated melanoma, the combination has higher activity to shrink their tumors, and with less side effects than the drugs on their own,” said Dr. Ribas, a researcher at the University of California, Los Angeles, Jonsson Comprehensive Cancer Center.
The FDA reviewed cobimetinib under its priority review program and gave the drug an orphan drug designation.
Cobimetinib (Cotellic) and vemurafinib (Zelboraf) are both marketed by Genentech.
On Twitter @karioakes
This article was updated November 16, 2015.