LBA2 - ALINA: Efficacy and safety of adjuvant alectinib versus chemotherapy in patients with early-stage ALK+ non-small cell lung cancer (NSCLC)

Background

For patients (pts) with resected, stage IB–IIIA, ALK+ NSCLC, the recommended treatment after surgery is platinum-based chemotherapy (CT), which is associated with modest improvements in survival. In advanced ALK+ NSCLC, alectinib is a preferred first-line treatment. Here, we report data from the prespecified interim analysis of ALINA (NCT03456076), a global, phase III, open-label, randomised trial assessing the efficacy and safety of adjuvant alectinib compared with CT in pts with completely resected ALK+ NSCLC.

Methods

Eligible pts were ≥18 years old, had an ECOG PS of 0/1 and completely resected, stage IB (≥4 cm)–IIIA, ALK+ NSCLC (per UICC/AJCC 7^th edition). Pts were randomised 1:1 to receive either oral alectinib 600 mg twice daily, or up to four 21-day cycles of IV platinum-based CT. Randomisation was stratified by stage (IB vs II vs IIIA) and race (Asian vs non-Asian). Alectinib was given for up to 24 months or until disease recurrence, unacceptable toxicity, or withdrawal of consent. Primary endpoint: investigator-assessed disease-free survival (DFS), tested hierarchically first in the stage II–IIIA and then in the ITT population (stage IB–IIIA). Other endpoints included: CNS-DFS, overall survival (OS), safety.

Results

A total of 257 pts were randomised to receive alectinib (n=130) or CT (n=127); baseline characteristics were overall well balanced between arms. At data cutoff (26 June 2023), median follow up was 27.8 months. A significant DFS benefit was observed with alectinib vs CT in both the stage II–IIIA (HR 0.24; 95% CI: 0.13–0.45) and ITT populations (HR 0.24; 95% CI: 0.13–0.43; Table). A clinically meaningful CNS-DFS benefit was observed in the ITT population (HR 0.22; 95% CI 0.08–0.58). OS data were immature. No unexpected safety findings were observed.

Conclusions

Alectinib is the first ALK inhibitor to significantly improve DFS compared with CT and provides an effective new treatment strategy for pts with resected ALK+ NSCLC. Table: LBA2

AEs, adverse events; NE, not estimable. ∗No Grade 5 AEs in either treatment arm

Clinical trial identification

NCT03456076.

Editorial acknowledgement

Third-party medical writing assistance was provided by Sean R Mills, 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

B.J. Solomon: Financial Interests, Personal, Invited Speaker: Roche/Genentech, Pfizer, AstraZeneca, Amgen, GSK; Financial Interests, Personal, Advisory Board: Roche/Genentech, Pfizer, Merck, Bristol Myers Squibb, AstraZeneca, Amgen, Lilly, Beigene, D3 Bio, Takeda, Janssen, GSK; Non-Financial Interests, Personal, Member of Board of Directors: Cancer Council of Victoria, Thoracic Oncology Group of Australasia, International Association for the Study of Lung Cancer; Financial Interests, Institutional, Research Grant: Sanofi ; Financial Interests, Institutional, Sponsor/Funding, Clinical trial funding to institution: Pfizer, Novartis, Roche/Genentech, Beigene, Lilly, Bristol Myers Squibb, Nuvalent, AstraZeneca. J.S. Ahn: Financial Interests, Personal, Invited Speaker: Takeda Pharm, Novartis Korea, Yuhan, Samyang, Amgen Korea, Boryung, BC World, Roche Korea, Menarini Korea, Pfizer, Lilly Korea, Boehringer Ingelheim, Kyowa Kirin, AstraZeneca Korea, Bayer Korea, Hanmi; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Role: Immuneoncia, Daiichi Sankyo Korea, Pharmbio Korea, Therapex, Guardant, Bayer Korea, Yooyoung, Vifor Pharma, Bixink. R. Dziadziuszko: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, Amgen; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Takeda, Novartis, MSD, Bristol Myers Squibb, Pfizer. F. Barlesi: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda, AbbVie, ACEA, Amgen, Eisai, Ignyta; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd., Innate Pharma, Mirati. M. Nishio: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceuticals, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, Lilly, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, Janssen. D.H. Lee: Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly ChongKeunDang, Janssen, MSD, Novartis, Ono, Pfizer, Roche, ST Cube, Takeda, BC World Pharm, Yuhan. H. Horinouchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche/Chugai, Amgen, AbbVie, Daiichi Sankyo, BMS, Ono, MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, AbbVie, Roche/Chugai, Daiichi- Sankyo, MSD, BMS, Ono, Janssen, Bayer, Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca, AbbVie, Daiichi Sankyo, BMS, Ono, Amgen; Financial Interests, Institutional, Principal Investigator: AstraZeneca, AbbVie, Roche/Chugai, MSD, BMS, Ono. M.J. Hochmair: Financial Interests, Personal, Invited Speaker: MSD, Roche, Lilly, AstraZeneca, Takeda; Financial Interests, Personal, Advisory Board: MSD, Roche, Lilly, AstraZeneca, Takeda. F. de Marinis: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Novartis, Roche/Genentech, MSD, Merck. M.R. Migliorino: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Takeda, AstraZeneca ; Financial Interests, Personal, Advisory Board: Pfizer. T.O. Lohmann: Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. T. Xu: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. A. Cardona Gavaldon: Financial Interests, Institutional, Stocks/Shares: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Full or part-time Employment: F. Hoffmann-La Roche Ltd. W. Bordogna: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. T. Ruf: Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd ; Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merck, MSD, Pfizer, Roche, Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim; Non-Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merck, MSD, Pfizer, Roche. All other authors have declared no conflicts of interest.