Alectinib has shown central nervous system (CNS) activity in phase II trials of previously treated ALK+ NSCLC. We report CNS efficacy data from the phase III ALUR study (NCT02604342) of alectinib vs standard relapse chemotherapy (CT) in pts with ALK+ NSCLC who previously failed platinum-based doublet CT and crizotinib.
Pts aged ≥18 years with ALK+ NSCLC, previously treated with CT and crizotinib were randomised 2:1 to alectinib (600mg twice daily) or CT (pemetrexed 500mg/m2 every three weeks [q3w] or docetaxel 75mg/m2 q3w) until disease progression (PD), death or withdrawal. After PD, pts could crossover from CT to alectinib. Primary endpoint was progression-free survival (PFS) by investigator assessment in the intent-to-treat (ITT) population. A key secondary endpoint was CNS overall response rate (CORR) by Independent Review Committee (IRC) in pts with measurable CNS mets at baseline (BL) (mC-ITT). Other CNS outcomes were CORR in pts with measurable and non-measurable CNS mets (C-ITT); 6-month cumulative incidence rate in the ITT, and C-ITT; CNS duration of response (CDOR) and disease control rate (CDCR); and safety.
In total, 107 pts were randomised (alectinib n = 72, CT n = 35; ITT) of whom 76 had BL CNS disease (alectinib n = 50, CT n = 26; C-ITT); 40 had measurable CNS mets (alectinib n = 24; CT n = 16; mC-ITT) and 36 had non-measurable CNS mets (alectinib n = 26, CT n = 10; nC-ITT). CNS efficacy endpoints are shown in the Table. The 6-month cumulative incidence rate of CNS PD was 11% (alectinib) vs 48% (CT) in the ITT, 15% vs 52% in the C-ITT and 0% vs 39% in pts without BL CNS disease. Safety and tolerability profile compared favourably for alectinib vs CT.
CNS-related outcomes were significantly improved with alectinib vs chemotherapy in previously treated ALK+ NSCLC. Alectinib reduces CNS PD and prevents the development of new CNS mets.Table:
1346P CNS efficacy endpoints
|C-ITT N = 76||mC-ITT N = 40|
|Alectinib N = 50||Chemotherapy N = 26||Alectinib N = 24||Chemotherapy N = 16|
|CORR, % (95% CI)||36||0||54.2||0|
|Difference (95% CI) P value||36% (13%–57%) p |
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche
J. de Castro: Membership on an advisory board: Astra-Zeneca, Boehringer, MSD, Novartis, Pfizer, Roche. S. Novello: Speaker Bureau: Eli Lilly, BMS, MSD, Astra Zeneca, Roche. J. Mazieres: Honoraria: Novartis, Roche, Pfizer, BMS, MSD. 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 speaker’s 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. F. de Marinis: Advisor for BMS, Pfizer, Roche, Astra Zeneca, BI. A. Zeaiter, A. Cardona, B. Balas: Employment with F. Hoffmann-La Roche. H. Johannsdottir: Employee of Hoffmann-La Roche. M. Chlistalla: Employee of F. Hoffmann-La Roche Ltd. V. Smoljanovic: Employee of F. Hoffmann-La Roche Ltd. with stock ownership. J. Wolf: Advisory boards and lecture fees from AstraZeneca, BMS, Boehringer-Ingelheim, Clovis, Lilly MSD, Novartis, Pfizer, Roche. Research support from BMS, MSD, Novartis, Pfizer, Roche. All other authors have declared no conflicts of interest.