Cobimetinib in combination with vemurafenib as a standard first-line approach improves survival in patients with BRAF V600 mutation-positive melanoma, updated results of the coBRIM study published in the journal The Lancet Oncology have shown.1
Previously reported findings from the phase 3 coBRIM study demonstrated that cobimetinib plus vemurafenib improves progression-free survival compared with placebo and vemurafenib in treatment-naïve patients with BRAF V600-mutant advanced melanoma. After longer follow-up, the investigators of the coBRIM study now report overall survival and additional safety results.
For the multicenter, double-blind study, investigators enrolled 495 adult patients with histologically confirmed BRAF V600 mutation-positive unresectable stage IIIC or IV melanoma. Participants were randomly assigned 1:1 to receive cobimetinib 60 mg orally once daily for 21 days followed by a 7-day rest period in each 28-day cycle or placebo, in combination with vemurafenib 960 mg orally twice daily.
At a median follow-up of 14.2 months, results showed that the updated investigator-assessed median progression-free survival was 12.3 months (95% CI, 9.5-13.4) for cobimetinib and vemurafenib compared with 7.2 months (95% CI, 5.6-7.5) for placebo and vemurafenib (hazard ratio [HR], 0.58; 95% CI, 0.46-0.72; P <.0001).
Researchers also found that median overall survival was 22.3 months (95% CI, 20.3-not estimable) for cobimetinib and vemurafenib vs 17.4 months (95% CI, 15.0-19.8) for placebo plus vemurafenib (HR, 0.70; 95% CI, 0.55-0.90; P =.005).
In terms of safety, no new safety signals were observed with longer follow-up. The most common grade 3 to 4 adverse events that occurred at a higher frequency in the cobimetinib group vs the placebo group were γ-glutamyl transferase elevation, blood creatine phosphokinase elevation, and alanine transaminase elevation.
Of note, serious adverse events were reported in 37% of cobimetinib-treated patients compared with 28% of those in the placebo arm.
1. Ascierto PA, McArthur GA, Dreno B, et al. Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016 Jul 29. doi: 10.1016/S1470-2045(16)30122-X. [Epub ahead of print]