Neoadjuvant and adjuvant pembrolizumab plus standard of care (SOC) in resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC): Exploratory efficacy analyses of the phase 3 KEYNOTE-689 study.

作者：Douglas Adkins, Robert I. Haddad, Yungan Tao, Christophe Le Tourneau, Nancy Y. Lee, Kunal K. Sindhu, 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, Cole Manschot, Kimberly Thomas Benjamin, Behzad Bidadi, Ravindra Uppaluri · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.6012 · 被引用次数：10 · 研究领域：Head and Neck Cancer Studies、Lung Cancer Treatments and Mutations、Colorectal and Anal Carcinomas

6012 Background: The addition of immune checkpoint inhibitors to neoadjuvant/adjuvant SOC has led to efficacy benefits across multiple tumor types. The randomized phase 3 KEYNOTE-689 study (NCT03765918) showed significantly improved event-free survival (EFS) with neoadjuvant/adjuvant pembrolizumab + SOC vs SOC alone for participants (pts) with resectable LA HNSCC independent of PD-L1 combined positive score (CPS ≥10 population: HR 0.66, 95% CI 0.49–0.88, P =.00217; CPS ≥1 population: HR 0.70, 95% CI 0.55–0.89, P =.00140; all pts: HR 0.73, 95% CI 0.58–0.92, P =.00411). We present exploratory efficacy endpoints for the intention-to-treat population of the study. Methods: Adults with SCC of the larynx/hypopharynx/oral cavity (stage III/IVA) or oropharynx (stage III/IVA p16− or stage III T4 N0-2 p16+) were randomized 1:1 to SOC (consisting of surgery + postoperative radiotherapy [PORT] ± concurrent cisplatin 100 mg/m 2 Q3W) with or without 2 cycles of neoadjuvant pembrolizumab, 3 cycles of pembrolizumab concurrent with PORT ± cisplatin and 12 cycles of adjuvant pembrolizumab (200 mg IV Q3W). The primary endpoint is EFS per RECIST 1.1 by blinded independent central review. Safety is a secondary endpoint. Prespecified exploratory efficacy endpoints include locoregional control (time from randomization to first locoregional radiographic progression or recurrence by imaging or biopsy), distant metastases-free survival (DMFS; time from randomization to first distant metastasis or deat...