1092PDAN UPDATE ON OVERALL SURVIVAL (OS) AND FOLLOW-ON THERAPIES IN BREAK-3, A PHASE III, RANDOMIZED TRIAL: DABRAFENIB (D) VS. DACARBAZINE (DTIC) IN PATIENTS (PTS) WITH BRAF V600E MUTATION-POSITIVE METASTATIC MELANOMA (MM)

ABSTRACT Aim: The primary analysis of BREAK-3 (NCT01227889) comparing progression-free survival in pts with BRAF V600E mutation-positive MM treated with D or DTIC was previously reported (Hauschild A, et al. Lancet 2012; 380:358–65). Median OS of D and DTIC last reported was 18.2 months (mo) (95% CI 16.6–NR) and 15.6 mo (95% CI 12.7–NR) at 14.4 mo median follow-up. Methods: From February to September 2011, 250 pts were enrolled at 93 centers globally. Pts were randomized to D and DTIC, 187 and 63 respectively; 37 (59%) of DTIC pts crossed over (xover) to D. After treatment discontinuation, pts were followed for OS and additional anticancer therapies. Pts could remain on D after disease progression (PD) at the investigator's discretion, with GSK approval. Results: OS hazard ratio (HR) was 0.77 (95% CI 0.52–1.13); median OS was 20.0 mo (95% CI 16.8–24.4) and 15.6 mo (95% CI 12.7–21.2) for D and DTIC, respectively, at 16.9 median mo follow-up. Estimated proportion alive was 45% vs. 32% at 2 years. Twenty-four (13%) of D pts and 3 (8%) of xover pts remained on D. No pts remained on DTIC. Out of these pts, 19/27 (70%) remained without PD on D. Median time on treatment for these 19 pts was 31.0 mo; (range 26.8–33.6 mo). Anticancer therapy after discontinuation of D was reported in 116 (62%) pts in D arm, including D (22%), ipilimumab (14%), DTIC (9%), vemurafenib (5%) and other therapies (12%). Anticancer therapy after discontinuation of DTIC was reported in 51 (81%) pts in DTIC arm, including D (60%), vemurafenib (10%), and ipilimumab (5%).The five most common adverse events (AEs) in D pts were hyperkeratosis (41%), arthralgia (37%), headache (36%), pyrexia (33%) and alopecia (29%). Serious AEs in ≥5% of D pts included cutaneous squamous-cell carcinoma/keratoacanthoma (10%) and pyrexia (5%). New non-cutaneous malignancies occurred in 4 (2%) pts taking D and 2 (5%) pts in xover pts vs. no events in the DTIC pts. Conclusions: Longer follow-up shows a stable HR for OS and safety profile. Median OS in the D arm was 20.0 mo vs. 15.6 mo in the DTIC arm. With approximately 60% of DTIC pts crossed over to D, it confounds effects of initial therapy on OS. Disclosure: A. Hauschild: Consult, Hon and Trial funding: Amgen,BMS,Celgene,Eisai,GSK,MelaSciences,Merck Serono,MSD/Merck,Novartis,Oncosec,Roche; J. Grobb: J-J. Grob has a compensated consultant or advisory relationship with GlaxoSmithKline, Roche, Bristol-Meyers Squibb, Merck and Celgene, and receives honoraria from GlaxoSmithKline and Roche; L. Demidov: L. Demidov is a consultant for GlaxoSmithKline, Merck and Roche, and receives support for clinical trials from Roche, Pfizer and Bristol Meyers-Squibb; T. Jouary: T. Jouary received personal fees and non-financial support from Roche, and provides expert testimony for GlaxoSmithKline IMS Health; R. Gutzmer: R. Gutzmer received support from GSK, honoraria from GSK, Roche, BSM, Novartis, MSD, Amgen, Almirall Hermal, LEO, Pfizer, Boehringer Ingelheim, Janssen, and participates in advisory boards for GSK, Roche, BMS, Novartis, MSD, Almirall Hermal and LEO; M. Millward: M. Millward receives clinical trial payments and participates in Advisory Boards for GlaxoSmithKline; P. Rutkowski: P. Rutkowski receives honoraria from GlaxoSmithKline, Roche and Bristol-Meyers Squibb, and participates in Advisory Boards for Roche, Bristol-Meyers Squibb and Novartis; C. Blank: C. Blank has an advisory role at GlaxoSmithKline, Roche, Bristol Meyers-Squibb, MSD and Novartia; W. Miller Jr.: W. Miller Jr received personal fees from Merck, Roche, Bristol-Meyers Squibb and Amgen; S. Martin-Algarra: Dr. Martin-Algarra reports personal fees for Advisory Boards and Lectures from GSK and fees fro Advisory Boards from Novartis, BMS and Roche; Chiarion Sileni: V. Chiarion Sileni receives compensation for advisory board participation from GlaxoSmithKline, Bristol-Meyers Squibb and Roche; G. Aktan: G. Aktan is an employee of GlaxoSmithKline and owns stock in the company; P. Haney: Pat Haney is an employee of GSK and has stock ownership and stock options; F. Jin: Fan Jin is an employee of GSK; J. Legos: Jeff Legos is a GSK employee and holds GSK shares; S. Swann: Suzanne Swann is a GSK employee and holds GSK stocks; P. Chapman: Glaxo Smith Kline: consulting fees, research support Genentech: consulting fees, research support. All other authors have declared no conflicts of interest.