Vemurafenib combined with cobimetinib is an effective treatment option for BRAF-mutant melanoma

This study examined the effectiveness and safety of the combined treatment of vemurafenib (Zelboraf) with cobimetinib (Cotellic) in advanced melanoma. Researchers concluded that this combination treatment is an important therapy option for patients with advanced melanoma.

Some melanoma patients have a mutation (permanant change) in the BRAF gene. BRAF inhibitors (such as vemurafenib) are used to treat these tumors. Although most patients have positive responses to these treatments, some patients do not see a response, such as tumor shrinkage. This can be due to drug resistance. This resistance happens due to the reactivation of the MAPK (a protein) pathway (allows the growth of the tumor). Adding a MAPK inhibitor to the treatment (such as cobimetinib) can help to overcome BRAF resistance.

A prior study investigated the effectiveness of this combination in advanced melanoma patients with BRAF mutation, for a period of 7.3 months. Vemurafenib combined with cobimetinib significantly improved progression-free survival (PFS; time from treatment to disease progression; 9.9 months) when compared to vemurafenib alone (6.2 months). The long-term outcomes associated with this treatment combination are not yet known. 

The objective of this study was to report effectiveness results, including overall survival and safety after a longer follow-up period.

495 patients were enrolled and randomly assigned to the combination group (247) or the vemurafenib alone group (248). The average follow-up period for PFS was 14.2 months. The average follow-up time for overall survival (time from treatment until death from any cause) was 18.5 months. 

The average PFS was 12.3 months in the combination group and 7.2 months in the vemurafenib alone group. Patients in the combination group were 42% less at risk of a worse PFS.

Average overall survival was 22.3 months for the combination group and 17.4 months for the vemurafenib alone group. Patients in the combination group were 30% less at risk of a worse survival.

85% of the patients in each group were evaluated for quality of life factors. Patients in the combination group had similar quality of life when compared to vemurafenib alone.

The combined treatment was tolerable and manageable. The most common moderate effects were an increase of certain liver enzymes (indicators of liver damage). 92 patients (37%) experienced severe side effects in the combination group and 69 (28%) in the vemurafenib alone group. Fever (2%) and dehydration (2%) were the most common severe effects in the combination group.

A total of 259 patients died, 117 (47%) in the combination group and 142 (58%) in the vemurafenib alone group.  

This study suggested that vemurafenib combined with cobimetinib was in patients with BRAF-mutated melanoma, with manageable side effects. 

This study was funded by F Hoffmann-La Roche-Genentech, the producer of cobimetinib.