First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients.

Background: Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or <1% in Part 1 of CheckMate 227. Here we report efficacy and safety results for the Asian subpopulation.
Methods: Patients with stage IV/recurrent NSCLC were randomized 1 : 1 : 1 to nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy (PD-L1 ≥1%) or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were evaluated among patients in Japan, South Korea, and Taiwan.
Results: In the Asian subpopulation with PD-L1 ≥1%, 81 patients received nivolumab plus ipilimumab and 81 received chemotherapy. Median OS was not reached with nivolumab plus ipilimumab versus 24.8 months with chemotherapy; 3-year OS rate was 53% versus 37% [hazard ratio (HR), 0.72; 95% confidence interval (CI) 0.47-1.11]. The 3-year progression-free survival rate was 26% versus 7% (HR, 0.65; 95% CI 0.45-0.96), objective response rate was 56% versus 37%, and median duration of response was 29.0 months (95% CI 15.0 months-not reached) versus 6.9 months (95% CI 3.9-11.1 months). Similar results were observed regardless of tumor PD-L1 expression and in Japanese patients. Grade 3-4 treatment-related adverse events occurred in 40% of patients receiving nivolumab plus ipilimumab and 36% receiving chemotherapy, in the overall Asian subpopulation (tumor PD-L1 expression ≥1% and <1%); no new safety signals were identified.
Conclusions: At 3-year follow-up, nivolumab plus ipilimumab provided durable long-term efficacy benefits versus chemotherapy regardless of tumor PD-L1 expression in the Asian subpopulation, including Japanese patients. Consistent with findings for all randomized patients, these data support the use of nivolumab plus ipilimumab as first-line treatment of Asian patients with advanced NSCLC.
Competing Interests: Role of the funder The study was designed by the steering committee and the funder. The funder contributed to data collection with the investigators, to data analysis and interpretation in collaboration with the authors, and to the writing of the report by funding professional medical writing assistance. All authors had full access to all the data in the study. Authors received no financial support or compensation for publication of this manuscript. Disclosure KJO: advisory board and/or speaker bureau and/or meeting travel/registration support from Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Janssen-Cilag, Merck Sharp & Dohme (MSD), Mundipharma, Natera, Novartis, Pfizer, Roche-Genentech, Teva, and TriStar; board member and shareholder: Carpe Vitae Pharmaceuticals; shareholder: DGC Diagnostics and RepLuca Pharmaceuticals; holds patents for novel therapeutics and diagnostic tests. KHL: advisory board: AstraZeneca, Bristol Myers Squibb, Eli Lilly, MSD, and Pfizer. KP: advisor/consultant: Bristol Myers Squibb. MN: consulting/advisory and/or honoraria and/or research funding: Abbvie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical Co. Ltd., Daichi Sankyo, Janssen, Lilly, Merck, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical Co. Ltd, Pfizer, Taiho Pharmaceutical Co. Ltd, Takeda, and Teijin Pharma. HS: research funding and/or honoraria: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Bristol Myers Squibb Japan, Chugai Pharmaceutical Co. Ltd., Merck KGaA, MSD K.K., Ono Pharmaceutical Co. Ltd, and Taiho Pharmaceutical Co. Ltd. YO: research funding and/or honoraria: Amgen, AstraZeneca, Boehringer Ingelheim, Celtrion, Chugai Pharmaceutical Co. Ltd, Eli Lilly, Janssen, Kissei, Kyorin, MSD, Nippon Kayaku, Novartis, Pfizer, Taiho Pharmaceutical Co. Ltd, and Takeda. TF: research funding: Bristol Myers Squibb. HD: honoraria: AstraZeneca, Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan, and Ono Pharmaceutical Co. Ltd. KH: research funding and/or honoraria: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical Co. Ltd, Lilly, MSD, Nippon Kayaku, Ono Pharmaceutical Co. Ltd, Pfizer, Taiho Pharmaceutical Co. Ltd, and Takeda. MT: honoraria: AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical Co. Ltd, Novartis, and Ono Pharmaceutical Co. Ltd. TY: research funding and/or honoraria: AstraZeneca, Boehringer Ingelheim Japan, Bristol Myers Squibb, Chugai Pharmaceutical Co. Ltd, Delta-Fly Pharma, Eli Lilly Japan, MSD K.K., Nippon Kayaku, Novartis K.K., Ono Pharmaceutical Co. Ltd, Pfizer Japan, Taiho Pharmaceutical Co. Ltd, and Takeda. FEN: employee of Bristol Myers Squibb; ownership/stockholder: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Gilead Sciences, and Johnson & Johnson. All other authors have declared no conflicts of interest. Data sharing Data are available upon reasonable request. Bristol Myers Squibb policy on data sharing may be found at https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)