Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma

作者：Ghassan K. Abou‐Alfa, George Lau, Masatoshi Kudo, Stephen L. Chan, Robin Kate Kelley, Junji Furuse, Wattana Sukeepaisarnjaroen, Yoon‐Koo Kang, Tu Van Dao, Enrico N. De Toni, Lorenza Rimassa, В. В. Бредер, Alexander Vasilyev, Alexandra Heurgué, Vincent C. Tam, Kabir Mody, Satheesh Chiradoni Thungappa, Yuriy Ostapenko, Thomas Yau, Sérgio Jobim Azevedo, Marı́a Varela, Ann‐Lii Cheng, Shukui Qin, Peter R. Galle, Sajid Ali, Michelle Marcovitz, Mallory Makowsky, Philip He, John F. Kurland, Alejandra Negro, Bruno Sangro · 发表于：NEJM Evidence · 年份：2022 · DOI：10.1056/evidoa2100070 · 被引用次数：1519 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer Immunotherapy and Biomarkers、Cancer Mechanisms and Therapy

BACKGROUND: A single, high priming dose of tremelimumab (anti-cytotoxic T lymphocyte–associated antigen 4) plus durvalumab (anti–programmed cell death ligand-1), an infusion regimen termed STRIDE (Single Tremelimumab Regular Interval Durvalumab), showed encouraging clinical activity and safety in a phase 2 trial of unresectable hepatocellular carcinoma. METHODS: In this global, open-label, phase 3 trial, the majority of the patients we enrolled with unresectable hepatocellular carcinoma and no previous systemic treatment were randomly assigned to receive one of three regimens: tremelimumab (300 mg, one dose) plus durvalumab (1500 mg every 4 weeks; STRIDE), durvalumab (1500 mg every 4 weeks), or sorafenib (400 mg twice daily). The primary objective was overall survival for STRIDE versus sorafenib. Noninferiority for overall survival for durvalumab versus sorafenib was a secondary objective. RESULTS: In total, 1171 patients were randomly assigned to STRIDE (n=393), durvalumab (n=389), or sorafenib (n=389). The median overall survival was 16.43 months (95% confidence interval [CI], 14.16 to 19.58) with STRIDE, 16.56 months (95% CI, 14.06 to 19.12) with durvalumab, and 13.77 months (95% CI, 12.25 to 16.13) with sorafenib. Overall survival at 36 months was 30.7%, 24.7%, and 20.2%, respectively. The overall survival hazard ratio for STRIDE versus sorafenib was 0.78 (96.02% CI, 0.65 to 0.93; P=0.0035). Overall survival with durvalumab monotherapy was noninferior to sorafenib (hazard...