1206MO - ALINA: Exploratory biomarker analyses in patients (pts) with resected ALK+ non-small cell lung cancer (NSCLC) treated with adjuvant alectinib vs chemotherapy (chemo)

Background

ALINA (NCT03456076) is a global, phase III, randomised trial evaluating efficacy and safety of adjuvant alectinib vs chemo in pts with resected stage IB (≥4 cm)–IIIA ALK+ NSCLC (AJCC 7^th ed.). A significant disease-free survival (DFS) benefit has been observed with alectinib vs chemo (hazard ratio: 0.24, 95% CI: 0.13–0.43, p<0.0001; intention-to-treat [ITT] population). We present exploratory biomarker analyses from baseline tissue samples and matched samples from pts recurring in the alectinib arm.

Methods

The biomarker-evaluable population (BEP) is a subpopulation of the ALINA ITT population, and includes pts who had sufficient baseline tumour tissue available for analysis and a valid result by the FoundationOne®CDx assay. Pts from China did not have baseline tissue available and were thus not included in the BEP.

Results

Baseline characteristics and DFS were similar in the ITT (N=257) and BEP (n=193). At data cut-off (Jun 2023), 13 (alectinib) and 41 (chemo) DFS events were observed in the BEP. In total, 81% of pts in the BEP had EML4-ALK fusions (most common: V1/V3; Table); alectinib showed DFS benefit vs chemo regardless of EML4 variant. CDKN2A, CDKN2B, TP53 and MTAP were the most commonly altered genes; CDKN2A, CDKN2B and MTAP alterations commonly co-occurred in single tumours. TP53 mutations were less prevalent in pts with early-stage NSCLC from ALINA (24%) than in pts with metastatic NSCLC from ALEX (NCT02075840) (41%). In the alectinib arm, pts with wild-type (WT) TP53 showed a trend for improved DFS vs pts with mutated TP53; this trend was not seen in the chemo arm. No correlation between DFS and CDKN2A, CDKN2B or MTAP alterations was observed for alectinib. No ALK on-target resistance mechanisms were identified in the recurrence analysis. Table: 1206MO

BEP, biomarker-evaluable population* Harbours multiple ALK-EML4 fusion variants¹ Camidge DR, et al. J Thorac Oncol 2019

Conclusions

In ALINA, DFS benefit with alectinib was seen regardless of EML4-ALK variant. Pts with WT TP53 at baseline showed a trend for improved DFS with alectinib vs mutated TP53.

Clinical trial identification

NCT03456076.

Editorial acknowledgement

This study is sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of authors, was provided by Rebecca Benatan, BSc, 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 and Institutional, Other, Consultant: Bristol Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Pfizer, Roche/Genentech, Amgen, Lilly, BeiGene, Takeda, GSK, Janssen; Financial Interests, Personal and Institutional, Other, Honoria: AstraZeneca, Merck Sharp & Dohme, Roche/Genentech, Pfizer, Amgen, Sanofi; Financial Interests, Personal, Royalties: UpToDate. Y. Wu: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Other, Consultant: AstraZeneca, Roche, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Other, Honoria: AstraZeneca, Roche, Pfizer, Boehringer Ingelheim, MSD Oncology, Bristol Myers Squibb, Hengrui Pharmaceutical, BeiGene; Financial Interests, Institutional, Research Funding: Boehringer Ingelheim, Roche, Pfizer, Bristol Myers Squibb. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, Amgen, Bristol Myers Squibb, GSK; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Novartis, Pfizer, MSD, Amgen. 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, Other, Honoria: Pfizer, Bristol Myers Squibb Japan, Ono Pharmaceutical, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Lilly, Nippon Kayaku, Takeda, Merck, Janssen, Amgen, Eisai, Daiichi Sankyo/UCB Japan. J.S. Ahn: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Role: Bayer, Yooyoung Pharmaceutical Co., Ltd, Pharmbio Korea, Guardant Health, Yuhan, ImmuneOncia, Therapex, Daiichi Sankyo Korea; Financial Interests, Institutional, Coordinating PI: Yuhan; Financial Interests, Institutional, Local PI: Roche, Yuhan; Financial Interests, Personal, Other, Honoria: Pfizer, Roche, BC World Pharmaceutical, Yuhan, Hamni, Novartis, JW Pharmaceutical, Amgen, Boehringer Ingelheim, Menarini, Kyowa Kirin, AstraZeneca, Bayer, Lilly, Takeda, Boryung, Nokwon Medical, Samyang. H. Horinouchi: Financial Interests, Personal, Other, Honoria: Lilly, Bristol Myers Squibb Japan, Kyowa Kirin, Chugai Pharma, AstraZeneca, MSD Oncology; Financial Interests, Institutional, Research Funding: Taiho Pharmaceutical, Merck Serono, Novartis, MSD Oncology, Chugai Pharma, Ono Pharmaceutical, A2 Healthcare, Daiichi Sankyo, BMKK, AbbVie, AstraZeneca. M.J. Hochmair: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, Lilly, AMGEN, Takeda; Financial Interests, Personal, Other, Consultant: Roche, BMS, MSD, Lilly, AMGEN, Takeda; Financial Interests, Personal, Speaker’s Bureau: Roche, BMS, MSD, Lilly, AMGEN, Takeda. M.R. Migliorino: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis Pharma, Roche, Takeda Oncology; Financial Interests, Personal, Other, Speaker grants: AstraZeneca, Novartis Pharma, Roche, Takeda Oncology. D. Planchard: Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Janssen, Pfizer, Roche, Pierre Fabre, Takeda, ArriVent, Mirati, Seagen; Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, AbbVie, Janssen, Pierre-Fabre, Takeda, ArriVent, Mirati, Seagen; Financial Interests, Personal, Funding, Travel/accommodation/expenses: AstraZeneca, Roche, Novartis, Pfizer; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Janssen, Pfizer, Roche, Pierre-Fabre, Takeda, ArriVent, Mirati, Seagen. K. Korphaisarn: Financial Interests, Institutional, Principal Investigator: Amgen, AstraZeneca, Beigene, Incyte, Merck Sharp & Dohme, Novartis, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Camber, Eisai, MSD, Novartis, Pfizer, Roche, Sanofi, Taiho, Servier, Takeda. J. Han: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen; Financial Interests, Personal, Advisory Role: Takeda, Merck, Novartis, Amgen, Abion, AbbVie, Oncobix; Financial Interests, Personal, Invited Speaker: Janssen, Novartis, Merck, Pfizer; Financial Interests, Personal, Sponsor/Funding: Pfizer, Roche, Takeda, ONO. T. Lohmann: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. A. Cardona Gavaldon: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks or ownership: F. Hoffmann-La Roche Ltd. V.R. Archer: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks or ownership: F. Hoffmann-La Roche Ltd. M. Nowicka: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. J. Noe: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche AG; Financial Interests, Personal, Stocks or ownership: F. Hoffmann-La Roche AG. All other authors have declared no conflicts of interest.