LBA38_PRDABRAFENIB IN PATIENTS WITH BRAF V600E-MUTANT ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC): A MULTICENTER, OPEN-LABEL, PHASE II TRIAL (BRF113928)

摘要: ABSTRACT Aim: Activating BRAF V600E mutations in NSCLC are present ≈1.5% of tumors, primarily adenocarcinomas, offering an opportunity to test targeted therapy for this disease. Methods: This single-arm, 2-stage design, Phase II study (NCT01336634) enrolled Stage IV V600E-mutant patients (pts) determined by local laboratory testing. Pts received dabrafenib 150 mg twice daily. Primary endpoint was investigator-assessed overall response rate (ORR) per RECIST 1.1. Results: As 30 April 2014, 84 pts (female 52%, median age 66 years [range 28–89], ECOG 0–1 86%, Asian 21%, never-smoker 37%, adenocarcinoma histology 96%) were from August 2011. Median duration on treatment 4.3 months (range, 0.3–25.2) with 21 (25%) still treatment. Six had not any prior regimen metastatic disease (first-line pts), 40 one line and 38 ≥2 lines (range 2–9). ORR 78 ≥ (second-line plus pts) 32% (n = 25, all partial responses [PRs]; 95% confidence interval [CI] 22–44%) control (DCR) >12 weeks 56% (95% CI 45–68%), (mDoR) 11.8 5.4–not reached) 48% responders progressed. Based assessment independent review committee (IRC), 64 second-line measurable disease; DCR 28% 18; 18–41%) 52% 39–64%) respectively, mDoR has been reached. Among the six first-line pts, three PR, four based IRC PRs. Most common (>25%) adverse events (AEs) pyrexia (36%), asthenia (30%), hyperkeratosis decreased appetite (29%), nausea (27%), cough (26%), fatigue (26%) skin papilloma (26%). Cutaneous squamous-cell carcinomas, including keratoacanthoma, reported 18%. Grade ≥3 AEs occurred 45% event grade 5 haemorrhage intracranial. Conclusions: Treatment mutated advanced demonstrated significant antitumor activity durable objective acceptable safety profile. Dabrafenib is first drug its class show a prospective trial mutations. Disclosure: D. Planchard: personal fees participating advisory boards AstraZeneca, BI, Lilly, Novartis, Pfizer, Roche BMS; E. Quoix: honoraria inclusion into GSK; G.J. Riely: G.J.R.'s institution grant GSK. G.J.R. Daiichi, Novartis Abbott consulting; F. Barlesi: M.A. Socinski: clinical support C. Tucker: employee C.T. owns stock B. Ma: Mookerjee: B.M. stocks Incyte Corporation AstraZeneca; C.M. Curtis, Jr: C.M.C.Jr B.E. Johnson: Roche/Genentech being expert witness; manufacture competitor (vemurafenib). B.E.J. KEW Group consultancy.All other authors have declared no conflicts interest.