Treatment-Free Survival Over 6 Years of Follow-up in Patients With Metastatic NSCLC Treated With First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in CheckMate 227 Part 1
- PMID: 40473108
- DOI: 10.1016/j.jtho.2025.05.019
Treatment-Free Survival Over 6 Years of Follow-up in Patients With Metastatic NSCLC Treated With First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in CheckMate 227 Part 1
Abstract
Introduction: Treatment-free survival (TFS) characterizes periods of disease control and durable clinical benefit after treatment discontinuation in patients treated with immunotherapy. In CheckMate 227 Part 1, nivolumab plus ipilimumab reported long-term durable overall survival (OS) benefit versus chemotherapy in patients with metastatic NSCLC. Here, we report updated long-term TFS results.
Methods: This analysis included all patients randomized (tumor programmed death ligand 1 [PD-L1] expression ≥1% and <1%). TFS was estimated as the restricted-mean survival time (between Kaplan-Meier curves for time to treatment discontinuation and time to subsequent systemic therapy or death) over 6 years after randomization. TFS was further divided into periods with or without ongoing toxicity (grade 3 or greater treatment-related adverse events) and estimated over 2 and 6 years after randomization.
Results: At 6 years after randomization (minimum follow-up: 73.5 months [∼6.1 years]), the estimated OS rate was 20% with nivolumab plus ipilimumab versus 11% with chemotherapy; 13% versus 2% of patients were treatment free. The 6-year mean TFS was 12.2 versus 5.0 months (difference 7.2 [95% confidence interval: 5.4-9.2]), with 17% versus 7% of the 6-year period spent in TFS. The 6-year mean TFS without grade 3 or greater treatment-related adverse events was 11.6 versus 4.8 months (difference, 6.9 [95% confidence interval: 5.1-8.9]). The proportion of mean TFS time increased from 15% of a 2-year to 17% of a 6-year period with nivolumab plus ipilimumab but decreased from 14% to 7% with chemotherapy. Similar results were observed by tumor PD-L1 expression.
Conclusions: Nivolumab plus ipilimumab improved TFS versus chemotherapy, regardless of tumor PD-L1 expression, supporting its use as an efficacious first-line treatment for metastatic NSCLC.
Keywords: Durability; First-line immunotherapy; Ipilimumab; Nivolumab; Treatment-free survival.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Disclosure Dr. Peters reports receiving institutional financial support for clinical trials from Amgen, Arcus, AstraZeneca, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, iTeos, Merck Sharp & Dohme, Mirati Therapeutics, PharmaMar, Pfizer, Promontory Therapeutics, Roche/Genentech, and Seattle Genetics; consulting fees to institution from AbbVie, Amgen, Arcus, AstraZeneca, Bayer, Beigene, BerGenBio, Bicycle Therapeutics, Biocartis, BioInvent, BioNTech, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly and Company, F-Star, Foundation Medicine, Genmab, Genzyme, Gilead Sciences, GlaxoSmithKline, Hutchmed, Illumina, Incyte Corporation, Ipsen, iTeos, Janssen, Qlucore, Merck Sharp & Dohme, Merck Serono, Merrimack, Mirati Therapeutics, Nuvation Bio, Nykode Therapeutics, Novartis, Novocure, PharmaMar, Promontory Therapeutics, Pfizer, Regeneron, Roche/Genentech, Sanofi, Seattle Genetics, Takeda, and Zymeworks; speaker’s fees to institution from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Foundation Medicine, GlaxoSmithKline, Illumina, Ipsen, Merck Sharp & Dohme, Mirati Therapeutics, Novartis, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, and Takeda; travel support to institution from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, and Takeda; fees to institution for participation on data safety monitoring board/advisory board for AbbVie, Amgen, Arcus, AstraZeneca, Bayer, Beigene, BerGenBio, Bicycle Therapeutics, Biocartis, BioInvent, BioNTech, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly and Company, F-Star, Foundation Medicine, Genmab, Genzyme, Gilead Sciences, GlaxoSmithKline, Hutchmed, Illumina, Incyte Corporation, Ipsen, iTeos, Janssen, Qlucore, Merck Sharp & Dohme, Merck Serono, Merrimack, Mirati Therapeutics, Nuvation Bio, Nykode Therapeutics, Novartis, Novocure, PharmaMar, Promontory Therapeutics, Pfizer, Regeneron, Roche/Genentech, Sanofi, Seattle Genetics, Takeda, and Zymeworks; and having a leadership role in Galenica SA (Board of Director). Ms. Regan reports receiving support for the present manuscript from Bristol Myers Squibb; research grants to institution from ETOP IBCSG Partners Foundation (including Biotheranostics, Novartis, Pfizer, and Roche), Bayer, and Bristol Myers Squibb; consulting fees from Bristol Myers Squibb, TerSera, and Tolmar; honoraria from Bristol Myers Squibb, Canadian Urological Association, McGill University funded by Merck, and St. Gallen Oncology Conferences; and participating on the data safety monitoring board of Austrian BCSG and on the advisory board of AstraZeneca, TerSera, and Tolmar. Dr. Paz-Ares reports receiving research grants from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, and Pfizer; consulting fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daichii Sankyo, Eli Lilly and Company, GlaxoSmithKline, Janssen, Merck KGaA (Darmstadt, Germany), Mirati Therapeutics, Merck Sharp & Dohme, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, and Takeda; honoraria from AstraZeneca, Janssen, Merck, and Mirati Therapeutics; and participating on the data safety monitoring/advisory board of Altum Sequencing and Genomica. Dr. Reck reports receiving consulting fees, honoraria, and travel support from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline, Janssen, Merck, Merck Sharp & Dohme, Mirati Therapeutics, Novartis, Pfizer, Roche, Regeneron, and Sanofi; and participating on the data safety monitoring/advisory board of Daiichi Sankyo and Sanofi. Dr. Borghaei reports serving as research support (clinical trials) for Amgen, Bristol Myers Squibb, and Eli Lilly and Company; advisory board/consultant to Amgen, AstraZeneca, Axiom, Bayer, Beigene, BerGenBio, BioNTech, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi, Eli Lilly and Company, EMD Serono, Genentech, Genmab, Grid Therapeutics, Guardant, IO Biotech, iTeos Therapeutics, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Pfizer, Natera, Novartis, Novocure, Oncocyte, PharmaMar, Puma, RAPT Therapeutics, Regeneron, and Takeda; serving on the data and safety monitoring board for the University of Pennsylvania CAR-T Program, Incyte Corporation, Novartis, SpringWorks Therapeutics, and Takeda; employee of Fox Chase Cancer Center; serving on scientific advisory board for Sonnet BioTherapeutics (with stock options); receiving stock options from Inspirna (formerly Rgenix) and Nucleai; receiving honoraria from Amgen, Daiichi, Pfizer, and Regeneron; and receiving travel support from Amgen, Bristol Myers Squibb, Eli Lilly and Company, EMD Serono, Genentech, Merck, Mirati Therapeutics, and Regeneron. Dr. O’Byrne reports receiving honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, Ipsen, Merck Group, Merck Sharp & Dohme, Pfizer/EMD Serono, Roche, Seagen, Takeda, and TriStar Technology Group; having a consulting/advisory role in Amgen, AstraZeneca/MedImmune, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Ipsen, Merck Sharp & Dohme, Pfizer, Roche/Genentech, Sanofi, and Seagen; receiving speaker fees from BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Janssen-Cilag, Merck Group, Merck Sharp & Dohme, Pfizer, Roche, and Seagen; receiving travel support from Bayer Holding and Sanofi; receiving payments to institution for being named on four active patents (two published and two provisional); and stock ownership in Carpe Vitae Pharmaceuticals, DGC Diagnostics, and RepLuca Pharmaceuticals. Dr. Brahmer reports receiving research grants from AstraZeneca and Bristol Myers Squibb; and having a consulting/advisory role in Amgen, AstraZeneca, Daiichi, GlaxoSmithKline, Janssen, Mestag Therapeutics, RAPT Therapeutics, and Summit Therapeutics. Dr. Penrod reports employment with and stock ownership in Bristol Myers Squibb at the time of study. Ms. Li reports employment with Bristol Myers Squibb. Dr. Tracy reports employment with Bristol Myers Squibb. Ms. Bushong reports employment with and stock ownership in Bristol Myers Squibb. Dr. Yuan reports employment with Bristol Myers Squibb. Mr. Lee reports employment with and stock ownership in Bristol Myers Squibb. Dr. Eccles reports employment with and stock ownership in Bristol Myers Squibb. Dr. Ray reports employment with Bristol Myers Squibb at the time of study. Dr. Ramalingam reports receiving research support to institution from Amgen, AstraZeneca, Bristol Myers Squibb, Merck, and Pfizer; travel support from AbbVie for advisory meeting; and participating on the data safety monitoring/advisory board of Gilead Sciences and Johnson & Johnson.
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