Camrelizumab plus rivoceranib vs sorafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): Final overall survival analysis of the phase 3 CARES-310 study.

Arndt Vogel Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany info_outline Arndt Vogel, Stephen Lam Chan, Zhenggang Ren, Yuxian Bai, Shanzhi Gu, Xiaoyan Lin, Zhendong Chen, Weidong Jia, Yongdong Jin, Yabing Guo, Xiaohua Hu, Alexander Valerievich Sultanbaev, Monika Pazgan-Simon, Margaryta Pisetska, Tsz Keung Nip, Haisong Zhang, Jinghua Du, Ann-Lii Cheng, Ahmed Omar Kaseb, Shukui Qin

Authors Arndt Vogel Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany info_outline Arndt Vogel, Stephen Lam Chan, Zhenggang Ren, Yuxian Bai, Shanzhi Gu, Xiaoyan Lin, Zhendong Chen, Weidong Jia, Yongdong Jin, Yabing Guo, Xiaohua Hu, Alexander Valerievich Sultanbaev, Monika Pazgan-Simon, Margaryta Pisetska, Tsz Keung Nip, Haisong Zhang, Jinghua Du, Ann-Lii Cheng, Ahmed Omar Kaseb, Shukui Qin Organizations Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany, Chinese University of Hong Kong, Hong Kong, China, Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China, Department of Gastroenterology, Harbin Medical University Cancer Hospital, Harbin, China, Department of Interventional Radiology, Hunan Cancer Hospital, Changsha, China, Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, China, Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China, Department of General Surgery, Anhui Provincial Hospital, Hefei, China, Department of Medical Oncology, Sichuan Cancer Hospital and Institute/The Affiliated Cancer Hospital School of Medicine, UESTC, Chengdu, China, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Liver Cancer Center, Guangzhou, China, Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China, State Autonomous Budgetary Healthcare Institution, Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan, Ufa, Russian Federation, Department of Infectious Disease and Hepatology, Wroclaw Medical University, and Centrum Badań Klinicznych P.Napora, Wroclaw, Poland, Department of Liver and Pancreas Gland Oncosurgery, Communal Non-profit Enterprise "Regional Center of Oncology", Kharkiv, Ukraine, Jiangsu Hengrui Pharmaceuticals, Co., Ltd, Shanghai, China, National Taiwan University Hospital, Taipei, Taiwan, Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, Cancer Center of Nanjing, Jinling Hospital, Nanjing, China Abstract Disclosures Research Funding No funding sources reported Background: The phase 3 CARES-310 trial is the first to demonstrate significant progression-free survival (PFS) and overall survival (OS) benefits with immunotherapy plus an anti-angiogenic tyrosine kinase inhibitor (TKI) over standard TKI as first-line treatment for uHCC. In the primary analysis of PFS (data cut-off [DCO], May. 10, 2021) and interim analysis of OS (DCO, Feb. 8, 2022), significant improvements were observed with camrelizumab (C; anti-PD-1 antibody) + rivoceranib (R; VEGFR2-TKI) vs . sorafenib (S). Here, we report updated data at the final analysis (FA), after an additional follow-up of ~16 mo. Methods: In this international, randomized, open-label, phase 3 trial, 543 patients with uHCC who had not previously received systemic treatment were randomized 1:1 to receive either C (200 mg, iv, q2w) + R (250 mg, po, qd) or S (400 mg, po, bid). As of Jun.14, 2023, 351 (65%) deaths occurred, and a protocol-specified FA was performed. Results: 272 patients were allocated to C+R and 271 to S. At DCO of FA, median follow-up was 22.1 mo in C+R group and 14.9 mo in S group. After end of study treatment, 36% of patients in C+R group and 42% in S group received subsequent targeted therapy; 17% and 36% received immunotherapy, respectively. Median OS was significantly prolonged with C+R vs . S (23.8 mo [95% CI 20.6-27.2] vs. 15.2 mo [95% CI 13.2-18.5]; hazard ratio (HR) 0.64 [95% CI 0.52-0.79]; 1-sided p <0.0001). OS rate with C+R vs. S was 49.0% vs. 36.2% at 24 mo, and 37.7% vs. 24.8% at 36 mo. OS benefits with C+R was generally consistent across subgroups, regardless of geographical region, race, and aetiology. Benefits in PFS, objective response rate (ORR) and duration of response (DoR) with C+R were also sustained after prolonged follow-up (Table). Safety data aligned with the interim OS analysis, with no new signals noted. Conclusions: At the protocol-specified FA, C+R continued to show clinically meaningful survival improvement compared with S, with manageable safety. The extended follow-up further confirmed the favorable benefit-to-risk profile of C+R, supporting it as a new first-line treatment option for uHCC. Clinical trial information: NCT03764293. Efficacy outcomes at FA. C+R (n=272) S (n=271) OS event, n (%) 159 (58.5) 192 (70.8) mOS (95% CI)*, mo 23.8 (20.6-27.2) 15.2 (13.2-18.5) HR (95% CI) † ; p value ‡ 0.64 (0.52-0.79); p <0.0001 PFS event, n (%) 199 (73.2) 209 (77.1) mPFS (95% CI)*, mo 5.6 (5.5-7.4) 3.7 (3.1-3.7) HR (95% CI) † ; p value ‡ 0.54 (0.44-0.67); p <0.0001 ORR (95% CI) 26.8 (21.7-32.5) 5.9 (3.4-9.4) mDoR (95% CI)*, mo 17.5 (9.3-NR) 9.2 (5.3-NR) PFS and tumor response were assessed by BIRC per RECIST v1.1. *Based on Kaplan-Meier method. † Based on stratified Cox proportional hazard model. ‡ One-sided p-value was calculated based on stratified log-rank test. NR, not reached.

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