Cobimetinib, Vemurafenib Improved Survival in BRAF V600–Mutated Melanoma

Combination treatment with cobimetinib and vemurafenib resulted in significantly improved overall and progression-free survival in patients with previously untreated BRAF V600–mutated advanced melanoma, according to updated efficacy results of the coBRIM trial published in Lancet Oncology.

“Patients treated with the combination of cobimetinib and vemurafenib achieved a higher objective response, longer progression-free survival, and longer overall survival compared with patients treated with vemurafenib alone,” wrote researchers led by Paolo A. Ascierto, MD, of the Istituto Nazionale Tumori Fondazione G Pascale in Naples, Italy. “The combination of cobimetinib and vemurafenib was recently approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of advanced BRAF V600–mutant melanoma and represents a new standard of treatment for patients with this disease.”

The double-blind coBRIM study enrolled 495 patients with BRAF V600–mutated unresectable melanoma and randomly assigned them to cobimetinib plus oral vemurafenib or placebo plus vemurafenib. Progression-free survival was the primary endpoint and overall survival was a secondary endpoint.

Previously reported results of the primary progression-free survival analysis showed that with a median follow-up of 7.3 months the combination treatment resulted in a significantly improved progression-free survival compared with vemurafenib alone (9.9 vs 6.2 months; P < .0001). In addition, 68% of patients in the combination arm achieved an objective response compared with 45% in the vemurafenib-alone arm (P < .0001).

The updated analysis had a median follow-up of 14.2 months. At this time, the investigator-assessed median progression-free survival was 12.3 months for patients assigned to cobimetinib and vemurafenib compared with 7.2 months for vemurafenib alone (P < .0001). Overall survival was also significantly better in patients assigned to the combination treatment (22.3 vs 17.4 months; P = .005).

“Moreover, the estimated landmark 2-year overall survival shows sustained benefit of the combination of cobimetinib and vemurafenib vs vemurafenib plus placebo,” the researchers wrote.

Seventy percent of patients assigned cobimetinib and vemurafenib had an objective response compared with 50% of patients on vemurafenib alone.

“The proportion of patients who achieved an overall response at the updated analysis were similar to those at the primary analysis; however, the proportions of patients achieving a complete response were higher at the updated analysis than at the primary analysis, indicating that some patients had an improved response with continued treatment,” the researchers wrote.

According to the study, the safety profile for cobimetinib and vemurafenib was manageable and tolerable, with no new safety signals observed with the longer follow-up period.

Commenting on the study, Nikhil I. Khushalani, MD, and Vernon K. Sondak, MD, of the Moffitt Cancer Center in Tampa, Florida, noted that the biomarker analyses of this study did not show any associations with survival, leaving clinicians “woefully unable to predict for individual patients with BRAF V600–mutant melanoma what the magnitude and duration of response to targeted therapy will be.”

“In view of the success of tolerable therapies for patients with advanced melanoma, referral patterns are changing, with patients coming to academic institutions only after failing to respond to standard therapy. However, if we are to realize hopes of routinely achieving cures in this disease, we need to better understand the interplay between host and tumor factors through trials going beyond the existing approved standards. International collaboration, as was evident in coBRIM, is a key step in this direction,” they added.