Paz-Ares, Luis GRamalingam, Suresh SCiuleanu, Tudor-EliadeLee, Jong-SeokUrban, LaszloCaro, Reyes BernabePark, KeunchilSakai, HiroshiOhe, YuichiroNishio, MakotoAudigier-Valette, ClarisseBurgers, Jacobus APluzanski, AdamSangha, RandeepGallardo, CarlosTakeda, MasayukiLinardou, HelenaLupinacci, LorenaLee, Ki HyeongCaserta, ClaudiaProvencio, MarianoCarcereny, EnricOtterson, Gregory ASchenker, MichaelZurawski, BogdanAlexandru, AureliaVergnenegre, AlainRaimbourg, JudithFeeney, KynanKim, Sang-WeBorghaei, HosseinO'Byrne, Kenneth JohnHellmann, Matthew DMemaj, ArteidNathan, Faith EllenBushong, JudithTran, PhuongBrahmer, Julie RReck, Martin2023-05-032023-05-032021-10-12http://hdl.handle.net/10668/22342In CheckMate 227, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with tumor programmed death-ligand 1 (PD-L1) greater than or equal to 1% (primary end point) or less than 1% (prespecified descriptive analysis). We report results with minimum 4 years' follow-up. Adults with previously untreated stage IV or recurrent NSCLC were randomized (1:1:1) to nivolumab plus ipilimumab, nivolumab, or chemotherapy (PD-L1 ≥1%); or to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 After 54.8 months' median follow-up, OS remained longer with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 greater than or equal to 1% (hazard ratio = 0.76; 95% confidence interval: 0.65-0.90) and PD-L1 less than 1% (0.64; 0.51-0.81); 4-year OS rate with nivolumab plus ipilimumab versus chemotherapy was 29% versus 18% (PD-L1 ≥1%); and 24% versus 10% (PD-L1 At more than 4 years' minimum follow-up, with all patients off immunotherapy treatment for at least 2 years, first-line nivolumab plus ipilimumab continued to demonstrate durable long-term efficacy in patients with advanced NSCLC. No new safety signals were identified. Immune-mediated AEs occurred early and resolved quickly with guideline-based management. Discontinuation of nivolumab plus ipilimumab due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/CTLA-4First-lineImmunotherapyMetastatic non–small cell lung cancerPD-1 checkpoint inhibitorAdultAntineoplastic Combined Chemotherapy ProtocolsHumansIpilimumabLung NeoplasmsNeoplasm Recurrence, LocalNivolumabresearch article34648948open access10.1016/j.jtho.2021.09.0101556-1380http://www.jto.org/article/S155608642103207X/pdf