Combination of vemurafenib and cobimetinib in advanced melanoma

The authors reviewed the effectiveness of combination therapy of vemurafenib (Zelboraf)­­ and cobimetinib (Cotellic) for the treatment of BRAF-mutated advanced melanoma. The study concluded that a combination treatment with vemurafenib and cobimetinib is an effective option in BRAF-mutant melanoma that cannot be removed by surgery. 

In advanced melanoma (stages 3 or 4), cancer spreads from the skin to other parts of the body.Targeted therapy has shown improved outcomes in these stages of the disease. Targeted therapies block specific genes, such as BRAF, that are often mutated in melanoma patients. 

BRAF inhibitors such as vemurafenib block certain proteins in BRAF-mutated melanoma cells. BRAF inhibitors have led to significant improvements in the treatment of melanoma, including melanoma that cannot be removed by surgery. However, patients can become resistant to BRAF inhibitors.  It is thought that a combination of therapies that inhibit different proteins may be more effective at delaying resistance than one inhibitor alone. Cobimetinib, for example, is a treatment that blocks the MEK protein.

The effect of combination therapy with BRAF and MEK inhibitors needs to be further evaluated.

The authors aimed to review the outcome of combination therapy of vemurafenib and cobimetinib in advanced melanoma.

In one phase III trial, stage 3 and 4 melanoma patients with BRAF mutations were included. The tumors of these patients could not be removed by surgery. None of the patients were previously treated. 247 patients received combination of vemurafenib and cobimetinib (group 1).  248 patients received placebo (harmless pill) plus vemurafenib (group 2).

At 14.9 months of follow-up, the average progression-free survival (the time following treatment before the disease progressed) was 12.3 months in group 1 and 7.2 months in group 2. Further, 16% of patients had complete disappearance of tumors and 54% of patients had partial disappearance of tumors. In group 2, 11% of patients had complete disappearance of tumors and 40% of patients had partial disappearance of tumors 

At 17.4 months follow-up, the overall survival (time from treatment until death from any cause) in group 1 was 22.3 months. This was compared to 17.4 months in group 2. The risk of death was reduced by 30% in group 1.

Adverse effects seen more often in patients treated with both cobimetinib and vemurafenib included diarrhea, nausea/vomiting, and sensitivity to light.

The authors concluded that combination treatment with vemurafenib and cobimetinib is an effective option in BRAF-mutant melanoma that cannot be removed by surgery.