"Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study"

作者全名："Qin, Shukui; Chan, Stephen L.; Gu, Shanzhi; Bai, Yuxian; Ren, Zhenggang; Lin, Xiaoyan; Chen, Zhendong; Jia, Weidong; Jin, Yongdong; Guo, Yabing; Hu, Xiaohua; Meng, Zhiqiang; Liang, Jun; Cheng, Ying; Xiong, Jianping; Ren, Hong; Yang, Fang; Li, Wei; Chen, Yajin; Zeng, Yong; Sultanbaev, Alexander; Pazgan-Simon, Monika; Pisetska, Margaryta; Melisi, Davide; Ponomarenko, Dmitriy; Osypchuk, Yurii; Sinielnikov, Ivan; Yang, Tsai-Sheng; Liang, Xiao; Chen, Chunxia; Wang, Linna; Cheng, Ann-Lii; Kaseb, Ahmed; Vogel, Arndt"

作者地址："[Qin, Shukui] Nanjing Univ Chinese Med, Jinling Hosp, Canc Ctr, Nanjing 210002, Peoples R China; [Qin, Shukui] Nanjing Med Univ, Nanjing 210002, Peoples R China; [Chan, Stephen L.] Chinese Univ Hong Kong, Hong Kong Canc Inst, Dept Clin Oncol, State Key Lab Translat Oncol, Hong Kong, Peoples R China; [Gu, Shanzhi] Hunan Canc Hosp, Dept Intervent Radiol, Changsha, Peoples R China; [Bai, Yuxian] Harbin Med Univ, Affiliated Tumor Hosp, Dept Gastroenterol, Harbin, Peoples R China; [Ren, Zhenggang] Fudan Univ, Zhongshan Hosp, Dept Hepat Oncol, Shanghai, Peoples R China; [Lin, Xiaoyan] Fujian Med Univ, Dept Oncol, Union Hosp, Fuzhou, Peoples R China; [Chen, Zhendong] Anhui Med Univ, Affiliated Hosp 2, Dept Oncol, Hefei, Peoples R China; [Jia, Weidong] Anhui Prov Hosp, Dept Gen Surg, Hefei, Peoples R China; [Jin, Yongdong] Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Sichuan Canc Ctr, Sch Med, Chengdu, Peoples R China; [Guo, Yabing] Southern Med Univ, Nanfang Hosp, Liver Canc Ctr, Dept Infect Dis, Guangzhou, Peoples R China; [Hu, Xiaohua] Guangxi Med Univ, Affiliated Hosp 1, Dept Med Oncol, Nanning, Peoples R China; [Meng, Zhiqiang] Fudan Univ, Dept Integrat Oncol, Shanghai Canc Ctr, Shanghai, Peoples R China; [Liang, Jun] Peking Univ Int Hosp, Dept Med Oncol, Beijing, Peoples R China; [Cheng, Ying] Jilin Canc Hosp, Dept Thorac Oncol, Jilin, Peoples R China; [Xiong, Jianping] Nanchang Univ, Affiliated Hosp 1, Dept Oncol, Nanchang, Peoples R China; [Ren, Hong] Chongqing Med Univ, Affiliated Hosp 2, Dept Infect Dis, Chongqing, Peoples R China; [Ren, Hong] Chongqing Med Univ, Inst Viral Hepatitis, Chongqing, Peoples R China; [Yang, Fang] Sixth Peoples Hosp Shenyang, Dept Hepatol, Shenyang, Peoples R China; [Li, Wei] First Hosp Jilin Univ, Canc Ctr, Jilin, Peoples R China; [Chen, Yajin] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Hepatobiliary Surg, Guangzhou, Peoples R China; [Zeng, Yong] Sichuan Univ, West China Hosp, Dept Thorac Oncol, Chengdu, Peoples R China; [Sultanbaev, Alexander] MoH Republ Bashkortostan, Dept Antitumor Drug Therapy, Republican Clin Oncol Dispensary, Ufa, Russia; [Pazgan-Simon, Monika] Wroclaw Med Univ, Dept Infecious Dis & Hepatol, Ctr Badan Klin Piotr Napora, Wroclaw, Poland; [Pisetska, Margaryta] Reg Ctr Oncol, Dept Liver & Pancreas Gland Oncosurg, Kharkiv, Ukraine; [Melisi, Davide] Azienda Osped Univ Integrata, Invest Canc Therapeut Clin Unit, Verona, Italy; [Melisi, Davide] Univ Verona, Digest Mol Clin Oncol Res Unit, Verona, Italy; [Ponomarenko, Dmitriy] State Budgetary Inst Healthcare Reg Oncol Dispens, Dept Chemotherapy, Irkutsk, Russia; [Osypchuk, Yurii] Odesa Reg Council, Communal Noncommercial Enterprise Odesa Reg Clin, Dept Surg, Odesa, Ukraine; [Sinielnikov, Ivan] Volyn Reg Council, Municipal Enterprise Volyn Reg Med Oncol Ctr, Dept Chemotherapy, Lutsk, Ukraine; [Yang, Tsai-Sheng] Linkou Chang Gung Mem Hosp, Dept Internal Med, Div Hematol Oncol, Chang Gung Med Fdn, Taoyuan, Taiwan; [Liang, Xiao; Chen, Chunxia; Wang, Linna] Jiangsu Hengrui Pharmaceut, Shanghai, Peoples R China; [Cheng, Ann-Lii] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan; [Kaseb, Ahmed] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA; [CARES-310 Study Grp] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany"

通信作者："Qin, SK (通讯作者)，Nanjing Univ Chinese Med, Jinling Hosp, Canc Ctr, Nanjing 210002, Peoples R China.; Qin, SK (通讯作者)，Nanjing Med Univ, Nanjing 210002, Peoples R China."

来源：LANCET

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001094086600001

JCR分区：Q1

影响因子：98.4

年份：2023

卷号：402

期号：10408

开始页：1133

结束页：1146

文献类型：Article

关键词：　

摘要："Background: Immunotherapy with immune checkpoint inhibitors combined with an anti-angiogenic tyrosine-kinase inhibitor (TKI) has been shown to improve overall survival versus anti-angiogenic therapy alone in advanced solid tumours, but not in hepatocellular carcinoma. Therefore, a clinical study was conducted to compare the efficacy and safety of the anti-PD-1 antibody camrelizumab plus the VEGFR2-targeted TKI rivoceranib (also known as apatinib) versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma.Methods: This randomised, open-label, international phase 3 trial (CARES-310) was done at 95 study sites across 13 countries and regions worldwide. Patients with unresectable or metastatic hepatocellular carcinoma who had not previously received any systemic treatment were randomly assigned (1:1) to receive either camrelizumab 200 mg intravenously every 2 weeks plus rivoceranib 250 mg orally once daily or sorafenib 400 mg orally twice daily. Randomisation was done via a centralised interactive response system. The primary endpoints were progression-free survival, as assessed by the blinded independent review committee per Response Evaluation Criteria in Solid Tumours version 1.1, and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drugs. We report the findings from the prespecified primary analysis for progression-free survival and interim analysis for overall survival. This study is registered with ClinicalTrials.gov (NCT03764293).Findings: Between June 28, 2019, and March 24, 2021, 543 patients were randomly assigned to the camrelizumab-rivoceranib (n=272) or sorafenib (n=271) group. At the primary analysis for progression-free survival (May 10, 2021), median follow-up was 7<middle dot>8 months (IQR 4<middle dot>1-10<middle dot>6). Median progression-free survival was significantly improved with camrelizumab-rivoceranib versus sorafenib (5<middle dot>6 months [95% CI 5<middle dot>5-6<middle dot>3] vs 3<middle dot>7 months [2<middle dot>8-3<middle dot>7]; hazard ratio [HR] 0<middle dot>52 [95% CI 0<middle dot>41-0<middle dot>65]; one-sided p<0<middle dot>0001). At the interim analysis for overall survival (Feb 8, 2022), median follow-up was 14<middle dot>5 months (IQR 9<middle dot>1-18<middle dot>7). Median overall survival was significantly extended with camrelizumab-rivoceranib versus sorafenib (22<middle dot>1 months [95% CI 19<middle dot>1-27<middle dot>2] vs 15<middle dot>2 months [13<middle dot>0-18<middle dot>5]; HR 0<middle dot>62 [95% CI 0<middle dot>49-0<middle dot>80]; one-sided p<0<middle dot>0001). The most common grade 3 or 4 treatment-related adverse events were hypertension (102 [38%] of 272 patients in the camrelizumab-rivoceranib group vs 40 [15%] of 269 patients in the sorafenib group), palmar-plantar erythrodysaesthesia syndrome (33 [12%] vs 41 [15%]), increased aspartate aminotransferase (45 [17%] vs 14 [5%]), and increased alanine aminotransferase (35 [13%] vs eight [3%]). Treatment-related serious adverse events were reported in 66 (24%) patients in the camrelizumab-rivoceranib group and 16 (6%) in the sorafenib group. Treatment-related death occurred in two patients: one patient in the camrelizumab-rivoceranib group (ie, multiple organ dysfunction syndrome) and one patient in the sorafenib group (ie, respiratory failure and circulatory collapse). Interpretation: Camrelizumab plus rivoceranib showed a statistically significant and clinically meaningful benefit in progression-free survival and overall survival compared with sorafenib for patients with unresectable hepatocellular carcinoma, presenting as a new and effective first-line treatment option for this population."

基金机构：Jiangsu Hengrui Pharmaceuticals; Elevar Therapeutics

基金资助正文：Jiangsu Hengrui Pharmaceuticals and Elevar Therapeutics.