Dacomitinib versus gefitinib for the first-line treatment of advanced EGFR mutation positive non-small cell lung cancer (ARCHER 1050): A randomized, open-label phase III trial.

Abstract

LBA9007 Background: Dacomitinib is a 2nd generation EGFR TKI with encouraging clinical activity as 1st-line therapy in patients with EGFR-activating mutation positive advanced NSCLC (Jänne, Lancet Oncol 2014). We performed the first randomized phase III trial, currently ongoing, comparing dacomitinib (D) with gefitinib (G) as 1st-line therapy (1L) (NCT01774721). Methods: Patients (pts) with newly diagnosed stage IIIB/IV/ recurrent NSCLC harboring an EGFR- activating mutation (exon 19 del or exon 21 L858R mu +/- exon 20 T790M mu) were randomized 1:1 to D 45 mg PO QD or G 250mg PO QD; stratification was by race and EGFR mutation subtype. The primary endpoint was PFS per blinded independent review (IRC) analyzed by Kaplan-Meier method with log-rank test and Cox model. Secondary endpoints included: overall survival, objective response rate (ORR), duration of response (DR), PFS per Investigator (INV), time to treatment failure (TTF), restricted mean survival time (RMST) for PFS, safety and patient-reported outcomes (PROs). Results: The ITT population included 452 pts with baseline characteristics fairly well balanced between the arms. ORR per IRC was similar between arms (75% [95% CI: 69, 80] for D and 72% [95% CI: 65, 77]; 2-sided p-value = 0.39; OS is not mature. The most commonly reported grade 3 adverse events with dacomitinib were dermatitis acneiform (13.7%) and diarrhea (8.4%) and with gefitinib ALT (8.5%); no new safety signals were identified. Conclusions: ARCHER 1050 was the first phase III head-to-head study of EGFR TKIs and demonstrated statistically significant and clinically meaningful improvement in efficacy of D vs. G in 1L NSCLC pts with EGFR-activating mutations with a manageable safety profile, to offer a new 1L treatment option. Clinical trial information: NCT01774721. [Table: see text]