Updated overall survival (OS) results for BRIM-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib (vem) with dacarbazine (DTIC) in previously untreated patients with BRAFV600E-mutated melanoma.

8502^ Background: We previously reported results of the planned OS interim analysis for BRIM-3 (50% of the planned 196 deaths required for final analysis) at which time the independent Data Safety Monitoring Board recommended release of results due to compelling efficacy (hazard ratio HR for death, 0. 37 95% CI 0. 26–0. 55) ; p<0. 0001 and PFS HR 0. 26 95% CI 0. 20–0. 33; p<0. 0001) and that DTIC-treated patients be permitted to cross over to receive vem. Median follow-up for vem patients was 3. 75 months, and longer follow-up would estimate median OS more reliably. Updated OS with median 6. 2 months follow-up and 199 total deaths showed HR for death 0. 44 (95% CI 0. 33–0. 59) favoring vem and median OS for vem not reached. We report here the results of an updated OS analysis performed in Nov 2011 with ~10 months median follow-up on vem. Methods: 675 patients with previously untreated, unresectable Stage IIIC or IV melanoma that tested positive for BRAF V600E mutation by the cobas 4800 BRAF V600 Mutation Test were randomized (1: 1) from Jan to Dec 2010 to vem (960 mg po bid) or DTIC (1000 mg/m 2 IV q3w). Co-primary endpoints were OS and PFS. OS data for DTIC patients who crossed over to vem were censored at the time of crossover. Results: Median lengths of follow-up on vem and DTIC were 10. 5 months (range 0. 4–18. 1) and 8. 4 months (range <0. 1–18. 3), respectively. There were 334 deaths. Median OS rates with vem and DTIC were 13. 2 months (95% CI 12. 0–15. 0) and 9. 6 months (95% CI 7. 9–11. 8), respectively. 12-month OS rates were 55% for vem and 43% for DTIC. HR for death was 0. 62 (95% CI 0. 49–0. 77) in favor of vem. 81 DTIC patients crossed over to vem. 44 (13%) vem and 65 (19%) DTIC patients received ipilimumab post-progression. Conclusions: With longer follow-up, vem treatment continues to be associated with improved OS in the BRIM-3 study. An updated analysis, with estimated median follow-up of ~13 months and including response data, will be conducted in Apr 2012 and presented at the meeting.