ALK+ NSCLC current standard of care is crizotinib. However, many pts experience progressive disease (PD) within a year, often in the central nervous system (CNS). Alectinib (ALC) has shown systemic and CNS efficacy in phase II trials of previously treated ALK+ NSCLC after crizotinib failure. The phase III ALUR study (NCT02604342) investigated efficacy and safety of ALC vs standard relapse chemotherapy (CT) in ALK+ NSCLC previously treated with platinum-based doublet CT and crizotinib.
Pts aged ≥18 years with previously treated ALK+ NSCLC were randomised 2:1 to ALC (600mg twice daily) or CT (pemetrexed 500mg/m2 q3w or docetaxel 75mg/m2 q3w) until PD, death or withdrawal. Crossover from CT to ALC was permitted after PD. Primary outcome was progression-free survival (PFS) by investigator (INV) assessment. Secondary outcomes included PFS by Independent Review Committee (IRC), overall response rate (ORR) and CNS ORR (CORR) by IRC, disease control rate (DCR), duration of response (DOR) and safety.
107 pts were randomised (ALC n = 72; CT n = 35); 104 received ≥1 dose of study drug (ALC n = 70; CT n = 34). At data cut-off (26.01.17) median follow-up: 6.5 months ALC, 5.8 months CT. Median treatment duration: 20.1 weeks ALC, 6.0 weeks CT. Median PFS by INV was 9.6 months (95% CI 6.9–12.2) ALC, 1.4 months (95% CI 1.3–1.6) CT (HR 0.15, 95% CI 0.08–0.29; p
ALC significantly improved systemic and CNS efficacy, including PFS and ORR, vs CT for previously treated ALK+ NSCLC, with a favourable safety profile vs CT.
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann - La Roche Ltd.
F. Hoffmann - La Roche Ltd.
S. Novello: Speaker Bureau: Eli Lilly, BMS, MSD, Astra Zeneca, Roche. J. Mazieres: Honoraria from Novartis, Roche, Pfizer, BMS, MSD. J. de Castro: Membership on an advisory board: Astra-Zeneca, Boehringer, MSD, Novartis, Pfizer, Roche. M.R. Migliorino: Honoraria and Advisory board: Bristol Mayer Squibb, Boehringer Ingelheim, MSD, Astra Zeneca. R. Dziadziuszko: Travel accommodation: Roche. Honoraria: Novartis, Tesaro, Clovis. Honoraria and speakers bureau: Pfizer, Honoraria and consulting role: Boehringer-Ingelheim, Astra-Zeneca, Ignyta. F. Griesinger: Advisory Board and corporate sponsored research: Roche, Astra Zeneca, Lilly, BMS, MSD, Celgene, Boehringer, Pfizer, Novartis. A. Kotb, A. Cardona, B. Balas, H. Johannsdottir, A. Das-Gupta: Employee of F. Hoffmann-La Roche Ltd. A. Zeiter: Employee of F. Hoffmann-La Roche Ltd. with stock ownership. J. Wolf: Advisory boards and lecture fees: AstraZeneca, BMS, Boehringer-Ingelheim, Clovis, Lilly, MSD, Novartis, Pfizer, Roche. Research support: BMS, MSD, Novartis, Pfizer, Roche. All other authors have declared no conflicts of interest.