Background: This phase III study (NCT01584648) of dabrafenib (D) + trametinib (T) compared with D + placebo (P) demonstrated superior progression-free survival (PFS) for D+T compared with D+P (HR = 0.75 ; 95% CI: 0.57–0.99; p = 0.035) in pts with BRAF V600E/K mutant, metastatic melanoma at the primary analysis (N Engl J Med 2014;371:1877). The interim overall survival (OS) favored D+T (40 deaths on D+T vs 55 on D+P), but did not cross the pre-planned stopping boundary for efficacy. Median time on study at the primary analysis was 9 months (0–16 months). Rates of adverse events (AEs) were similar for both arms. More pts had AEs leading to dose modifications with D+T vs D+P, and fewer hyperproliferative skin AEs were reported with D+T. The study was continued after the primary analysis to evaluate OS without crossover from D+P to D+T. Methods: Pts were randomized 1:1 to receive D (150mg twice daily) + T (2mg once daily) or D+P as first-line therapy. Eligible pts were age 18 or older, ECOG performance status ≤ 1, and had histologically confirmed unresectable stage IIIC or IV, BRAF V600E/K mutant cutaneous melanoma. The primary endpoint was investigator-assessed PFS; secondary endpoints were OS, overall response rate (ORR), duration of response (DoR), and safety. The final statistical OS comparison was to be initiated when 220 events were reported. Results: From May 2012 to January 2013, 423 pts were randomized (211 to D+T, 212 to D+P). The 220th death was reported on Jan 12, 2015; analysis is expected to be completed in Mar 2015. Estimated median time on study at data cut off is 20 months (0-31 months). Conclusions: The statistical analysis will evaluate the superiority of D+T vs D+P for OS. A 2-year OS landmark analysis, updated PFS, ORR, DoR, and safety will be presented. Clinical trial information: NCT01584648