Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study

Abstract

Background: The ALEX study demonstrated significantly improved progression-free survival (PFS) with alectinib versus crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC) at the primary data cut-off (9 February 2017). We report mature PFS (cut-off: 30 November 2018) and overall survival (OS) data up to 5 years (cut-off: 29 November 2019).

Patients and methods: Patients with stage III/IV ALK-positive NSCLC were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151) until disease progression, toxicity, withdrawal or death. Primary end point: investigator-assessed PFS. Secondary end points included objective response rate, OS and safety.

Results: Mature PFS data showed significantly prolonged investigator-assessed PFS with alectinib [hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.32-0.58; median PFS 34.8 versus 10.9 months crizotinib]. Median duration of OS follow-up: 48.2 months alectinib, 23.3 months crizotinib. OS data remain immature (37% of events). Median OS was not reached with alectinib versus 57.4 months with crizotinib (stratified HR 0.67, 95% CI 0.46-0.98). The 5-year OS rate was 62.5% (95% CI 54.3-70.8) with alectinib and 45.5% (95% CI 33.6-57.4) with crizotinib, with 34.9% and 8.6% of patients still on study treatment, respectively. The OS benefit of alectinib was seen in patients with central nervous system metastases at baseline [HR 0.58 (95% CI 0.34-1.00)] and those without [HR 0.76 (95% CI 0.45-1.26)]. Median treatment duration was longer with alectinib (28.1 versus 10.8 months), and no new safety signals were observed.

Conclusions: Mature PFS data from ALEX confirmed significant improvement in PFS for alectinib over crizotinib in ALK-positive NSCLC. OS data remain immature, with a higher 5-year OS rate with alectinib versus crizotinib. This is the first global randomized study to show clinically meaningful improvement in OS for a next-generation tyrosine kinase inhibitor versus crizotinib in treatment-naive ALK-positive NSCLC.

Clinical trials number: NCT02075840.

Keywords: ALK-positive; alectinib; crizotinib; non-small-cell lung cancer; overall survival; progression-free survival.

Conflict of interest statement

Disclosure TM declares a leadership role with Sanonics Ltd, Hutchinson ChiMed and AstraZeneca; honoraria/consulting fees from ACEA Biosciences, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb (BMS), Celgene, Chimed, Cirina, Fishawack Facilitate, Ignyta, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme (MSD), Novartis, OncoGenex, Pfizer, Roche/Genentech, SFJ Pharmaceutical, Takeda and Vertex; and research funding from AstraZeneca, BMS, Clovis Oncology, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceutical and XCovery. DRC declares honoraria/consulting fees from Abbvie, Ariad, Array, Celgene, Clovis Oncology, Eli Lilly, Genoptix, G1 Therapeutics, Novartis, Orion and Roche/Genentech. SMG declares honoraria/consulting fees from Ariad, AstraZeneca, BMS, Pfizer and Roche/Genentech. RR has nothing to disclose. RD declares honoraria/consulting fees from Roche, Pfizer, Novartis, Boehringer-Ingelheim, AstraZeneca, Takeda, Yuhan, XCovery, SeattleGenetics and Celon Pharma. DWK declares non-financial support from Roche for travel to meetings for the study, and provision of writing assistance, medicines, equipment or administrative support; and non-financial support from Amgen and Daiichi-Sankyo for travel to advisory meetings. His institution has received funding from Alpha Biopharma, AstraZeneca/Medimmune, Boehringer-Ingelheim, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, XCovery and Yuhan. MP declares honoraria/consulting fees from Roche/Genentech, Pfizer, Eli Lilly, Boehringer-Ingelheim, Clovis Oncology, MSD, Chugai, BMS, Amgen, Novartis, Pierre Fabre, AstraZeneca and Takeda; and institutional grants for clinical/translational research from Roche, AstraZeneca, Chugai and Takeda. SHIO declares honoraria/consultancy fees from ARIAD, AstraZeneca, Pfizer, Roche/Genentech and TP Therapeutics; speakers' bureau participation for ARIAD, AstraZeneca and Roche/Genentech; research funding from ARIAD, AstraZeneca, Daiichi Sankyo, Pfizer and Roche/Genentech; and stock ownership in TP Therapeutics. JSA declares honoraria from Pfizer, AstraZeneca, Menarini, Roche, Eisai, Boehringer-Ingelheim, BMS-Ono, MSD, Janssen, Samsung Bioepis, Takeda and Amgen. ATS is currently an employee of Novartis and has received honoraria or consulting fees from F. Hoffmann La-Roche Ltd, Genentech, Pfizer, Novartis, Ariad, Ignyta, Daiichi-Sankyo, Taiho, Blueprint medicines, LOXO, EMD Serono and Foundation medicine. WB, VS, MH, JN and TR are employees of F. Hoffmann-La Roche Ltd. SP declares educational grants or honoraria for advisory board attendance and/or lectures from Abbvie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer-Ingelheim, BMS, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Roche, Foundation Medicine, Illumina, Janssen, MSD, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics and Takeda.

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.