Five-Year Outcomes of Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer From the Randomized KEYNOTE-671 Study.

BACKGROUND: Adding perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved survival outcomes compared with neoadjuvant chemotherapy and surgery alone in participants with early-stage non-small-cell lung cancer (NSCLC) in the phase 3, randomized KEYNOTE-671 study. We report results from KEYNOTE-671 after 5 years of follow-up. PATIENTS AND METHODS: Eligible participants with previously untreated, resectable stage II, IIIA, or IIIB (N2) NSCLC were randomized 1:1 to 4 cycles of pembrolizumab 200 mg or placebo every 3 weeks, plus platinum-doublet chemotherapy, followed by surgery then adjuvant pembrolizumab or placebo every 3 weeks for up to 13 cycles. Dual primary endpoints were event-free survival (EFS) per RECIST v1.1 by investigator assessment and overall survival (OS). RESULTS: 797 participants were randomized to pembrolizumab (n=397) or placebo (n=400). Median time from randomization to data cutoff (July 3, 2025) was 60.4 (range, 42.6‒85.8) months. Five-year EFS was 49.9% (95% CI, 44.6‒55.0) in the pembrolizumab arm and 26.5% (95% CI, 21.7‒31.5) in the placebo arm (HR, 0.58; 95% CI, 0.48‒0.69); 5-year OS was 64.6% (95% CI, 59.5‒69.2) and 53.6% (95% CI, 48.3‒58.6), respectively (HR, 0.74; 95% CI, 0.59‒0.92). No detriment to health-related quality of life was identified in the pembrolizumab versus placebo arm with longer follow-up. Safety was consistent with the known profiles of each treatment. CONCLUSIONS: After 5 years of follow-up, EFS was nearly double with perioperative pembrolizumab plus neoadjuvant chemotherapy, along with continued improvement in OS compared with neoadjuvant chemotherapy and surgery alone. The durable and clinically meaningful benefits observed support use of this treatment as a standard of care for patients with resectable early-stage NSCLC (ClinicalTrials.gov, NCT03425643).