Overall survival and objective response in advanced unresectable hepatocellular carcinoma: A subanalysis of the REFLECT study

作者：Masatoshi Kudo, Richard S. Finn, Shukui Qin, Kwang‐Hyub Han, Kenji Ikeda, Ann‐Lii Cheng, Arndt Vogel, Francesco Tovoli, Kazuomi Ueshima, Hiroshi Aikata, Carlos López, Marc Pracht, Zhiqiang Meng, Bruno Daniele, Joong‐Won Park, D. Palmer, Toshiyuki Tamai, Kenichi Saito, Corina E. Dutcus, Riccardo Lencioni · 发表于：Journal of Hepatology · 年份：2022 · DOI：10.1016/j.jhep.2022.09.006 · 被引用次数：56 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Statistical Methods in Clinical Trials、Breast Cancer Treatment Studies

BACKGROUND & AIMS: Validated surrogate endpoints for overall survival (OS) are important for expediting the clinical study and drug-development processes. Herein, we aimed to validate objective response as an independent predictor of OS in individuals with unresectable hepatocellular carcinoma (HCC) receiving systemic anti-angiogenic therapy. METHODS: We investigated the association between objective response (investigator-assessed mRECIST, independent radiologic review [IRR] mRECIST and RECIST v1.1) and OS in REFLECT, a phase III study of lenvatinib vs. sorafenib. We conducted landmark analyses (Simon-Makuch) of OS by objective response at 2, 4, and 6 months after randomization. RESULTS: Median OS was 21.6 months (95% CI 18.6-24.5) for responders (investigator-assessed mRECIST) vs. 11.9 months (95% CI 10.7-12.8) for non-responders (hazard ratio [HR] 0.61; 95% CI 0.49-0.76; p <0.001). Objective response by IRR per mRECIST and RECIST v1.1 supported the association with OS (HR 0.61; 95% CI 0.51-0.72; p <0.001 and HR 0.50; 95% CI 0.39-0.65; p <0.001, respectively). OS was significantly prolonged for responders vs. non-responders (investigator-assessed mRECIST) at the 2-month (HR 0.61; 95% CI 0.49-0.76; p <0.001), 4-month (HR 0.63; 95% CI 0.51-0.80; p <0.001), and 6-month (HR 0.68; 95% CI 0.54-0.86; p <0.001) landmarks. Results were similar when assessed by IRR, with both mRECIST and RECIST v1.1. An exploratory multivariate Cox regression analysis identified objective response by...