Vemurafenib in patients with BRAF V600 mutation–positive metastatic melanoma: final overall survival results of the randomised BRIM-3 study

Abstract

Background: The BRIM-3 trial showed improved progression-free survival (PFS) and overall survival (OS) for vemurafenib compared with dacarbazine in treatment-naive patients with BRAF^V600 mutation–positive metastatic melanoma. We present final OS data from BRIM-3.Patients and methods: Patients were randomly assigned in a 1:1 ratio to receive vemurafenib (960 mg twice daily) or dacarbazine (1000 mg/m² every 3 weeks). OS and PFS were co-primary endpoints. OS was assessed in the intention-to-treat population, with and without censoring of data for dacarbazine patients who crossed over to vemurafenib.Results: Between January 4, 2010 and December 16, 2010, a total of 675 patients were randomised to vemurafenib (n = 337) or dacarbazine (n = 338, of whom 84 crossed over to vemurafenib). At the time of database lock (August 14, 2015), median OS, censored at crossover, was significantly longer for vemurafenib than for dacarbazine (13.6 months [95% confidence interval (CI) 12.0–15.4] versus 9.7 months [95% CI 7.9–12.8; hazard ratio (HR) 0.81 [95% CI 0.67–0.98]; P = 0.03), as was median OS without censoring at crossover (13.6 months [95% CI 12.0–15.4] versus 10.3 months [95% CI 9.1–12.8]; HR 0.81 [95% CI 0.68–0.96]; P = 0.01). Kaplan-Meier estimates of OS rates for vemurafenib versus dacarbazine were 56% versus 46%, 30% versus 24%, 21% versus 19% and 17% versus 16% at 1, 2, 3 and 4 years, respectively. Overall, 173 of 338 patients (51%) in the dacarbazine arm and 175 of 337 (52%) of those in the vemurafenib arm received subsequent anticancer therapies, most commonly ipilimumab. Safety data were consistent with the primary analysis.Conclusions: Vemurafenib continues to be associated with improved median OS in the BRIM-3 trial after extended follow-up. OS curves converged after ≈3 years, likely as a result of crossover from dacarbazine to vemurafenib and receipt of subsequent anticancer therapies.ClinicalTrials.gov: NCT01006980.

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