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

• Published in: Journal of hepatology 2023-01, Vol.78 (1), p.133-141
• Main Authors: Kudo, Masatoshi, Finn, Richard S., Qin, Shukui, Han, Kwang-Hyub, Ikeda, Kenji, Cheng, Ann-Lii, Vogel, Arndt, Tovoli, Francesco, Ueshima, Kazuomi, Aikata, Hiroshi, López, Carlos López, Pracht, Marc, Meng, Zhiqiang, Daniele, Bruno, Park, Joong-Won, Palmer, Daniel, Tamai, Toshiyuki, Saito, Kenichi, Dutcus, Corina E., Lencioni, Riccardo
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Carcinoma, Hepatocellular - pathology; Humans; landmark analysis; lenvatinib; Liver Neoplasms - pathology; mRECIST; response status; Retrospective Studies; Sorafenib - therapeutic use; surrogate endpoint
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2022.09.006

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. 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. 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