Final PFS, updated OS and safety data from the randomised, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC

Background We report mature PFS, updated OS and safety data from the global phase III ALEX study (NCT02075840) of ALC vs CRZ in patients (pts) with untreated ALK+ NSCLC after a further 12 months (m) of follow-up (cutoff date: 30 Nov 2018). Methods Eligible pts had stage IIIB/IV ALK+ NSCLC (by central IHC), ECOG PS 0–2 and no prior systemic therapy for advanced NSCLC. Asymptomatic CNS metastases (mets) were allowed. Pts were randomised 1:1 to twice-daily ALC 600mg (n = 152) or CRZ 250mg (n = 151). Primary endpoint: investigator (INV)-assessed PFS (RECIST v1.1), with q8w CNS imaging in all pts. Results Mature, median INV-assessed PFS: 34.8 m (95% CI 17.7–NR) ALC vs 10.9 m (95% CI 9.1–12.9) CRZ (ITT stratified HR 0.43, 95% CI 0.32–0.58; p Conclusions This final updated PFS analysis confirms the superior efficacy and favourable tolerability of ALC compared with CRZ in pts with untreated ALK+ NSCLC. OS data remain immature (stratified HR 0.69, 95% CI 0.47–1.02), with a 4-year OS rate of 64.5% (95% CI 55.6–73.4) with ALC. Table . 1484PD PFS event-free rate, % (95% CI) OS event-free rate, % (95% CI) ALC (n = 152) CRZ (n = 151) ALC (n = 152) CRZ (n = 151) Duration (years) Overall Baseline CNS mets Overall Baseline CNS mets Overall Overall Yes No Yes No 1 67.8 (60.3–75.3) 58.5 74.5 48.0 (39.7–56.2) 32.5 57.2 84.3 (78.4–90.2) 82.5 (76.1–88.9) 2 56.6 (48.6–64.6) 52.0 59.8 24.8 (17.6–32.1) 6.3 35.7 72.5 (65.1–79.9) 65.1 (56.7–73.4) 3 46.4 (38.2–54.5) 40.5 50.6 13.5 (7.7–19.3) 2.1 20.2 66.9 (59.0–74.8) 56.7 (47.8–65.6) 4 43.7 (35.4–51.9) 38.0 47.6 NE (NE–NE) NE NE 64.5 (55.6–73.4) 52.2 (42.6–61.8) NE, not estimable Clinical trial identification NCT02075840. Editorial acknowledgement Nicola Griffin of Gardiner-Caldwell Communications; funded by F. Hoffmann-La Roche. Legal entity responsible for the study F. Hoffmann-La Roche Ltd. Funding F. Hoffmann-La Roche Ltd. Disclosure T.S.K. Mok: Leadership role: Sanonics Ltd.; Honoraria (self), Advisory / Consultancy: ACEA Biosciences, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chimed, Cirina, Fishawack Facilitate, Ignyta, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, OncoGenex, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, SFJ Pharm; Research grant / Funding (self): AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Merck Sharp & Dohme, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, SFJ Pharmaceutical and XCovery. A.T. Shaw: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd, Genentech, Pfizer, Novartis, Ariad, Ignyta, Daiichi-Sankyo, Taiho, Blueprint medicines, LOXO, EMD Serono and Foundation medicine. R.D. Camidge: Honoraria (self), Advisory / Consultancy: AbbVie, Ariad, Array, Celgene, Clovis Oncology, Eli Lilly, Genoptix, G1 Therapeutics, Novartis, Orion, and F. Hoffmann-La Roche Ltd/Genentech. S.M. Gadgeel: Honoraria (self), Advisory / Consultancy: Ariad, AstraZeneca, Bristol-Myers Squibb, Pfizer and F. Hoffmann-La Roche Ltd/Genentech. R. Dziadziuszko: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd, Pfizer, Boehringer Ingelheim, Clovis Oncology, Novartis, AstraZeneca and Tesaro. D. Kim: Travel / Accommodation / Expenses: F. Hoffmann-La Roche Ltd, Pfizer, Boehringer Ingelheim, Clovis Oncology, Novartis, AstraZeneca and Tesaro; Travel / Accommodation / Expenses: Novartis Oncology; Research grant / Funding (institution): Alpha Biopharma, AstraZeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery and Yuhan. M. Perol: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Merck Sharp & Dohme, Chugai, Bristol-Myers Squibb, Amgen, Novartis, Pierre Fabre, AstraZeneca, Takeda ; Research grant / Funding (institution): F. Hoffmann-La Roche Ltd, AstraZeneca, Chugai and Takeda. S. Ou: Honoraria (self): ARIAD, AstraZeneca, Pfizer, F. Hoffmann-La Roche Ltd/Genentech and TP Therapeutics; Speaker Bureau / Expert testimony: ARIAD, AstraZeneca and F. Hoffmann-La Roche Ltd/Genentech; Research grant / Funding (self): ARIAD, AstraZeneca, Daiichi Sankyo, Pfizer and F. Hoffmann-La Roche Ltd/Genentech; Shareholder / Stockholder / Stock options: TP Therapeutics. W. Bordogna: Full / Part-time employment: F. Hoffmann-La Roche Ltd. V. Smoljanovic: Full / Part-time employment: F. Hoffmann-La Roche Ltd. M. Hilton: Full / Part-time employment: F. Hoffmann-La Roche Ltd. S. Peters: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche Ltd, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Nova. All other authors have declared no conflicts of interest.