Perioperative Pembrolizumab for Early-Stage Non–Small-Cell Lung Cancer

作者：Heather A. Wakelee, Moïshe Liberman, Terufumi Kato, Masahiro Tsuboi, Se‐Hoon Lee, Shugeng Gao, Ke‐Neng Chen, Christophe Dooms, Margarita Majem, E. Eigendorff, Gastón Lucas Martinengo, Olivier Bylicki, Delvys Rodríguez‐Abreu, Jamie E. Chaft, Silvia Novello, Jing Yang, Steven M. Keller, Ayman Samkari, Jonathan Spicer · 发表于：New England Journal of Medicine · 年份：2023 · DOI：10.1056/nejmoa2302983 · 被引用次数：1082 · 研究领域：Lung Cancer Diagnosis and Treatment、Cancer Immunotherapy and Biomarkers、Cancer, Stress, Anesthesia, and Immune Response

BACKGROUND: Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone. METHODS: We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety. RESULTS: A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P<0.001). The estimated 24...