LBA11 - Alectinib (ALC) vs crizotinib (CRZ) in Asian patients (pts) with treatment-naïve advanced <italic>ALK</italic>+ non-small cell lung cancer (NSCLC): 5-year update from the phase III ALESIA study

Background

ALC is approved as first-line (1L) treatment for advanced ALK+ NSCLC based on the global Phase 3 ALEX study, which reported a significant PFS benefit for ALC vs CRZ (HR 0.43, 95% CI 0.32–0.58) and a clinically meaningful improvement in 5-year OS (62.5 vs 45.5%). Primary analysis of ALESIA confirmed PFS benefit of 1L ALC in Asian pts with advanced ALK+ NSCLC; we present updated data from ALESIA (cutoff date: 16 May 2022) after ≥5 years follow-up.

Methods

Pts had stage IIIB/IV ALK+ NSCLC by central IHC and ECOG PS 0–2. Asymptomatic CNS metastases (mets) were allowed. Pts were randomised 2:1 to ALC 600mg BID (n=125) or CRZ 250mg BID (n=62), stratified by ECOG PS (0/1 vs 2) and baseline CNS mets (yes vs no). Regular tumour/CNS imaging was performed. Primary endpoint: PFS by investigator (INV). Secondary endpoints included: time to CNS progression, ORR, DOR, OS and safety.

Results

At the updated data cutoff (median duration of follow-up 61 months [m] ALC, 51 m CRZ), a durable PFS benefit was seen for ALC vs CRZ (HR 0.33, 95% CI 0.23–0.49; median PFS [INV] 41.6 vs 11.1 m) and a clinically meaningful improvement in OS (HR 0.60, 95% CI 0.37–0.99; 5-year OS rate 66.4 vs 56.0%; pts remaining at risk 69 vs 25). PFS/OS benefit of ALC occurred in pts with or without CNS mets at baseline (Table) and across pre-specified subgroups. More CRZ pts (77.1 vs 61.8% ALC) received ≥1 anti-cancer therapy post-PD, with ALC the most widely used ALK TKI. Asymptomatic CNS PD was more common in CRZ pts (25.8 vs 10.4% ALC); treatment beyond asymptomatic CNS PD was longer with ALC vs CRZ (median 11.2 vs 3.9 m). ALC had a favourable safety profile vs CRZ despite longer treatment duration (42.3 vs 12.6 m), with fewer Grade 3–5 AEs (48 vs 55%), serious AEs (28 vs 29%) or AEs leading to treatment discontinuation (11 vs 15%).

Conclusions

With ≥5 years follow-up, 1L alectinib 600mg BID continues to provide clinical benefit to Asian pts with advanced ALK+ NSCLC, with no new safety concerns. Table: LBA11

mets, metastases; NE, not evaluable; pts, patients.

Clinical trial identification

NCT02838420.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Fiona Duthie, PhD, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

C. Zhou: Financial Interests, Personal, Invited Speaker: Roche, Lily China, Hengrui, Qilu, MSD, C—Stone. Y. Lu: Non-Financial Interests, Personal, Invited Speaker: BeiGene, Roche/Genentec, AstraZeneca, Pfizer; Non-Financial Interests, Personal, Advisory Role: Roche/Genentech, AstraZeneca, Pfizer, Bristol Myers Squibb, Merck Sharp & Dohme, BeiGene; Non-Financial Interests, Personal, Leadership Role: Roche/Genentech, AstraZeneca, BeiGene. S. Kim: Non-Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Janssen, Norvatis, Takeda; Financial Interests, Personal, Research Grant: Yuhan; Non-Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Norvatis, Takeda, Yuhan. T. Baisamut (reungwetwattana): Financial Interests, Personal, Advisory Board, and speaker: Astrazeneca, Pfizer, Roche, MSD, Novartis, BMS, Amgen; Financial Interests, Personal, Advisory Board: Yuhan; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, Novartis, MSD. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Merck, Pfizer, Lilly; Financial Interests, Personal, Research Grant: AstraZeneca, Merck. L. Bu: Financial Interests, Personal, Full or part-time Employment: Roche. L. Qian: Financial Interests, Personal, Full or part-time Employment: Roche Pharma Product Development China. V.R. Archer: Financial Interests, Personal, Full or part-time Employment: Roche Productslimited. M. Hilton: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. M. Zhou: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. L. Zhang: Financial Interests, Personal, Research Grant: AZ, BMS, Roche; Financial Interests, Personal, Principal Investigator: Noratis, Hansoh pharm, KeLun Pharm, QiLu pharm. All other authors have declared no conflicts of interest.