First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE‑048

• Published in: International journal of clinical oncology 2024-12, Vol.29 (12), p.1825-1839
• Main Authors: Oridate, Nobuhiko, Takahashi, Shunji, Tanaka, Kaoru, Shimizu, Yasushi, Fujimoto, Yasushi, Matsumoto, Koji, Yokota, Tomoya, Yamazaki, Tomoko, Takahashi, Masanobu, Ueda, Tsutomu, Hanai, Nobuhiro, Yamaguchi, Hironori, Hara, Hiroki, Yoshizaki, Tomokazu, Yasumatsu, Ryuji, Nakayama, Masahiro, Shiga, Kiyoto, Fujii, Takashi, Mitsugi, Kenji, Takahashi, Kenichi, Nohata, Nijiro, Gumuscu, Burak, Lerman, Nati, Tahara, Makoto
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; B7-H1 Antigen - antagonists & inhibitors; Cancer Research; Cell death; Cell survival; Cetuximab - administration & dosage; Cetuximab - therapeutic use; Chemotherapy; East Asian People; Female; Follow-Up Studies; Head and neck carcinoma; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - pathology; Humans; Hypopharynx; Japan; Larynx; Male; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; NCT; NCT02358031; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Oncology; Oral cavity; Original; Original Article; Oropharynx; PD-L1 protein; Pembrolizumab; Progression-Free Survival; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - mortality; Squamous Cell Carcinoma of Head and Neck - pathology; Surgical Oncology
• ISSN: 1341-9625; 1437-7772; 1437-7772
• DOI: 10.1007/s10147-024-02632-x

Background Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up. Methods Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. Results In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2–81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13–1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34–1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27–1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27–2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56–2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57–2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. Conclusion After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. Clinical trial registration NCT02358031.