Alectinib versus crizotinib in treatment-naive advanced ALK-positive non-small cell lung cancer (NSCLC): Primary results of the global phase III ALEX study.
Invited conference paper presented and published in conference proceedings


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AbstractBackground: Alectinib, a TKI targeting ALK, has shown robust efficacy in crizotinib-naïve/resistant ALK+ NSCLC. J-ALEX showed superiority of alectinib 300mg BID vs crizotinib in Japanese pts with crizotinib-naïve ALK+ NSCLC (progression-free survival [PFS] HR 0.34, p<0.0001). We report primary results from the ALEX study of first-line alectinib 600mg BID vs crizotinib in advanced ALK+ NSCLC (NCT02075840). Methods: This open-label randomized multicenter phase III study enrolled pts with stage IIIB/IV ALK+ NSCLC, determined by central IHC testing. Eligible pts had ECOG PS 0–2 and no prior systemic therapy for advanced NSCLC. Pts with asymptomatic CNS metastases were allowed. Pts (n=303) were randomized 1:1 to receive alectinib 600mg or crizotinib 250mg BID. Primary endpoint: Investigator (Inv)-assessed PFS (RECIST v1.1), with systematic CNS imaging in all pts. Secondary endpoints included independent review committee (IRC)-assessed PFS, IRC-assessed time to CNS progression (TTP), objective response rate (ORR), overall survival (OS) and safety. Results: At the primary data cut-off (9 Feb 2017), alectinib demonstrated statistically significant superiority vs crizotinib, reducing risk of progression/death by 53% (HR 0.47, 95% CI 0.34–0.65, p<0.0001); alectinib median PFS was not reached (95% CI 17.7–NE) vs crizotinib 11.1 months (95% CI 9.1–13.1). Key secondary endpoints showed superiority for alectinib vs crizotinib, respectively: IRC PFS, HR 0.50 (95% CI 0.36–0.70; p<0.0001); median PFS 25.7 months (95% CI 19.9–NE) vs 10.4 months (95% CI 7.7–14.6); CNS TTP, cause-specific HR of CNS progression 0.16 (95% CI 0.10–0.28; p<0.0001); ORR (Inv) 83% (95% CI 76–89) vs 76% (95% CI 68–82), p=0.09; OS, based on 25% events, HR 0.76 (95% CI 0.48–1.20; p=0.24). Grade 3/4 AEs were less frequent with alectinib, 41%, vs 50% with crizotinib; fatal AEs occurred in 3% vs 5%, respectively. Rates of AEs leading to discontinuation, dose reduction and interruption were lower with alectinib. Conclusions: Alectinib showed superior efficacy and favorable tolerability compared with crizotinib. ALEX results support alectinib as a new standard of care for treatment-naïve ALK+ NSCLC. Funding: F. Hoffmann-La Roche Clinical trial information
All Author(s) ListAlice Tsang Shaw, Solange Peters, Tony Mok, Shirish M. Gadgeel, Jin Seok Ahn, Sai-Hong Ignatius Ou, Maurice Perol, Rafal Dziadziuszko, Dong-Wan Kim, Rafael Rosell, Ali Hassan Zeaiter, Ting Liu, Sophie Golding, Bogdana Balas, Johannes Noé, Peter N. Morcos, D. Ross Camidge
Name of Conference2017 ASCO Annual Meeting
Start Date of Conference02/06/2017
End Date of Conference06/06/2017
Place of ConferenceChicago, Illinois
Country/Region of ConferenceUnited States of America
Proceedings TitleJournal of Clinical Oncology
Series TitleLung Cancer—Non-Small Cell Metastatic, Oral Abstract Session
Number in SeriesLBA9008
Year2017
Volume Number35
LanguagesEnglish-United Kingdom

Last updated on 2018-18-01 at 11:19