As reported by Ascierto et al in The Lancet Oncology, longer-term follow-up in the pivotal phase III coBRIM trial confirmed the benefit of adding cobimetinib to vemurafenib (Zelboraf) in first-line treatment of BRAF V600–mutant unresectable stage IIIC or IV melanoma. Grant A. McArthur, FRACP, of the University of Melbourne, is the corresponding author of The Lancet Oncology article.
In the double-blind trial, 495 patients were randomized to receive cobimetinib (n = 247; 60 mg once daily for 21 days followed by 7 days off in each 28-day cycle) or placebo (n = 248) in combination with vemurafenib (960 mg twice daily). Progression-free and overall survival rates were the primary and secondary endpoints.
Median follow-up in the updated analysis was 14.2 months. Median investigator-assessed progression-free survival was 12.3 months in the combination group vs 7.2 months in the vemurafenib group (hazard ratio [HR] = 0.58, P < .0001). The final analysis for overall survival occurred when 52% of patients had died (August 2015). Median overall survival was 22.3 months vs 17.4 months (HR = 0.70, P = .005).
No new safety signals for the combination were observed over longer follow-up. The most common grade 3 or 4 adverse events occurring more frequently in the combination group were increased γ-glutamyl transferase (15% vs 10%), increased creatine phosphokinase (12% vs < 1%), and increased alanine transaminase (11% vs 6%). Serious adverse events occurred in 37% vs 28%, with pyrexia (2%) and dehydration (2%) being the most common in the cobimetinib/vemurafenib group.
The investigators concluded: “These data confirm the clinical benefit of cobimetinib combined with vemurafenib and support the use of the combination as a standard first-line approach to improve survival in patients with advanced BRAF V600–mutant melanoma.”
The study was funded by F. Hoffmann-La Roche–Genentech. ■
Ascierto PA, et al: Lancet Oncol 17:1248-1260, 2016.