1. 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.
- Author
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Mok T, Camidge DR, Gadgeel SM, Rosell R, Dziadziuszko R, Kim DW, Pérol M, Ou SI, Ahn JS, Shaw AT, Bordogna W, Smoljanović V, Hilton M, Ruf T, Noé J, and Peters S
- Subjects
- Anaplastic Lymphoma Kinase genetics, Humans, Progression-Free Survival, Protein Kinase Inhibitors therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Crizotinib therapeutic use, Lung Neoplasms drug therapy, Lung Neoplasms genetics
- 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., Competing Interests: 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.)
- Published
- 2020
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