Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer

作者：Ravindra Uppaluri, Robert I. Haddad, Yungan Tao, Christophe Le Tourneau, Nancy Y. Lee, William H. Westra, Rebecca D. Chernock, Makoto Tahara, Kevin J. Harrington, A L Klochikhin, Irene Braña, Gustavo Vasconcelos Alves, Brett Hughes, Marc Oliva, Iane Pinto Figueiredo Lima, Tsutomu Ueda, Tomasz A. Rutkowski, Ursula C. Schroeder, Paul‐Stefan Mauz, Thorsten Fuereder, Simon Laban, Nobuhiko Oridate, Aron Popovtzer, Nicolas Mach, Yevhen Korobko, Diogo Alpuim Costa, Anupama Hooda-Nehra, Cristina P. Rodriguez, R. Bryan Bell, Cole Manschot, Kimberly Benjamin, Burak Gümüşçü, Douglas Adkins · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2415434 · 被引用次数：323 · 研究领域：Head and Neck Cancer Studies、Esophageal Cancer Research and Treatment、Cancer Immunotherapy and Biomarkers

BACKGROUND: The benefit of the addition of perioperative pembrolizumab to standard care with surgery and adjuvant therapy for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) is unclear. METHODS: In this phase 3, open-label trial, we randomly assigned participants with locally advanced HNSCC in a 1:1 ratio to receive 2 cycles of neoadjuvant pembrolizumab and 15 cycles of adjuvant pembrolizumab (both at a dose of 200 mg every 3 weeks) in addition to standard care (pembrolizumab group) or standard care alone (control group). Standard care was surgery and adjuvant radiotherapy with or without concomitant cisplatin. The primary end point was event-free survival, sequentially assessed in participants whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS) of 10 or more (CPS-10 population), participants whose tumors expressed PD-L1 with a CPS of 1 or more (CPS-1 population), and all the participants. A higher CPS indicates a higher proportion of cells that express PD-L1. RESULTS: A total of 363 participants (234 with a CPS of ≥10 and 347 with a CPS of ≥1) were assigned to the pembrolizumab group and 351 (231 with a CPS of ≥10 and 335 with a CPS of ≥1) to the control group. Surgery was completed in approximately 88% of the participants in each group. At the first interim analysis, the median follow-up was 38.3 months. Event-free survival at 36 months was 59.8% in the pembrolizumab group and 45.9% in the control group ...