Combination of vemurafenib and cobimetinib in melanoma

The authors evaluated the effectiveness of a combination therapy of vemurafenib (Zelboraf)­­ and cobimetinib (Cotellic) for the treatment of advanced melanoma.

In advanced melanoma (stage 3/4), 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 attack specific genes such as BRAF. These genes are often mutated in melanoma patients and lead to cancer growth. BRAF inhibitors are targeted therapies that stop certain cell signaling proteins (e.g. MAPK and MEK) in BRAF mutated melanoma cells. Vemurafenib is an example of a BRAF inhibitor.

BRAF inhibitors have led to significant improvements in the treatment of melanoma. However, patients often become resistant to BRAF inhibitors. This can lead to secondary cancer. A combination of BRAF and MEK inhibitors has been shown to delay the development of resistance. Cobimetinib is an example of MEK inhibitor.

The effect of combination therapy with BRAF and MEK inhibitors needs to be further evaluated for deciding appropriate treatment options in advanced melanoma. 

The authors aimed to analyze the effectiveness of combination therapy with BRAF and MEK inhibitors in advanced melanoma.

495 patients were included in this study. All had previously untreated advanced melanoma. Patients were randomly assigned to one of two groups. Group 1 received a combination treatment of vemurafenib and cobimetinib. Group 2 received vemurafenib and placebo (substance with no therapeutic effect).

The average progression-free survival (time following treatment before the disease progressed) was 9.9 months in group 1. This was compared to 6.2 months in group 2. 68% of patients in group 1 had complete or partial disappearance of tumors. This was compared to 45% in group 2. The overall survival (time from treatment until death from any cause) over a 9-month period was 81% in group 1. This was compared to 73% in group 2. There were non-significant but higher incidents of severe or life-threatening adverse events in group 1 (13%) compared to group 2 (9%).

The authors concluded that addition of cobemitinib to vemurafenib significantly improved progression-free survival in BRAF-mutant advanced melanoma patients.