Authors: Patrick M. Forde, M.B., B.Ch., Ph.D., Jonathan D. Spicer, M.D., Ph.D., Mariano Provencio, M.D., Ph.D., Tetsuya Mitsudomi, M.D., Ph.D., Mark M. Awad, M.D., Ph.D., Changli Wang, M.D., Shun Lu, M.D., Ph.D., Enriqueta Felip, M.D., Ph.D., Scott J. Swanson, M.D., Julie R. Brahmer, M.D., Keith Kerr, M.B., Ch.B., Janis M. Taube, M.D., Tudor-Eliade Ciuleanu, M.D., Ph.D., Fumihiro Tanaka, M.D., Ph.D., Gene B. Saylors, M.D., Ke-Neng Chen, M.D., Ph.D., Hiroyuki Ito, M.D., Ph.D., Moishe Liberman, M.D., Ph.D., Claudio Martin, M.D., Stephen Broderick, M.D., Lily Wang, M.D., Junliang Cai, M.D., Quyen Duong, Ph.D., Stephanie Meadows-Shropshire, Ph.D., Joseph Fiore, Pharm.D., Sumeena Bhatia, Ph.D., and Nicolas Girard, M.D., Ph.D., for the CheckMate 816 Investigators

Published June 2, 2025 N Engl J Med 2025;393:741-752 DOI: 10.1056/NEJMoa2502931

VOL. 393 NO. 8

Abstract
 

Background

Neoadjuvant nivolumab plus chemotherapy significantly improved pathological complete response and event-free survival in patients with resectable non–small-cell lung cancer (NSCLC) in a phase 3 trial. Data are needed on overall survival.
 

Methods

In this open-label, phase 3 trial, patients with stage IB to IIIA resectable NSCLC were randomly assigned to receive nivolumab plus chemotherapy or chemotherapy alone for three cycles, followed by surgery. The primary end points were event-free survival and pathological complete response. Here, we report the results of the planned analysis of overall survival.

Results

A total of 358 patients were concurrently assigned to receive nivolumab plus chemotherapy (179 patients) or chemotherapy alone (179 patients). The final analysis of overall survival significantly favored neoadjuvant nivolumab plus chemotherapy over chemotherapy (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.523 to 0.998; P=0.048). At a median follow-up of 68.4 months, the 5-year overall survival was 65.4% with nivolumab plus chemotherapy and 55.0% with chemotherapy alone, with consistency across most subgroups. In exploratory analyses, the 5-year overall survival in the nivolumab-plus-chemotherapy group was 95.3% (95% CI, 82.7 to 98.8) among the patients with a pathological complete response and 55.7% (95% CI, 46.9 to 63.7) among those without such a response; survival was 75.0% among the patients with presurgery clearance of circulating tumor DNA (ctDNA) and 52.6% among those without such clearance. No new safety signals were observed.
 

Conclusions

Three cycles of neoadjuvant nivolumab plus chemotherapy significantly improved overall survival among patients with resectable NSCLC as compared with chemotherapy alone. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.)