Vemurafenib in patients with BRAFV600 mutation–positive metastatic melanoma: final overall survival results of the randomised BRIM-3 study
Mené sur 675 patients atteints d'un mélanome métastatique présentant la mutation BRAFV600, cet essai de phase III compare l'efficacité, du point de vue de la survie globale et de la survie sans progression, de la dacarbazine et du vémurafénib
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 BRAFV600 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.