Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial

Clinical Cancer Research - Tập 27 Số 4 - Trang 1003-1011 - 2021
Jianming Xu1, Jie Shen2, Shanzhi Gu3, Yun Zhang1, Lihua Wu4, Jian Wu4, Guoliang Shao5, Yanqiao Zhang6, Li Xu7, Tao Yin8, Jingfeng Liu9, Zhenggang Ren10, Jianping Xiong11, Xianhai Mao12, Ling Zhang13, Jiayin Yang14, Le‐Qun Li15, Xiaohong Chen16, Zhiming Wang17, Kangsheng Gu18, Xi Chen19, Zhanyu Pan20, Kuansheng Ma21, Xinmin Zhou22, Zujiang Yu23, Enxiao Li24, Guowen Yin25, Xiao Zhang26, Shuni Wang26, Quanren Wang26
11Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China.
22Department of Oncology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
33Radioactive Interventional Department, Hunan Cancer Hospital, Changsha, China.
44Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
55Intervention Therapy Department, Zhejiang Cancer Hospital, Hangzhou, China.
66Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
77Hepatobiliary and Pancreatic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China.
88Department of Hepatic & Biliary & Pancreatic Surgery, Hubei Cancer Hospital, Affiliated Hubei Cancer Hospital of Huazhong University of Science and Technology, Wuhan, China.
99Liver Department, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.
1010Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
1111Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
1212Liver Surgery, Hunan People's Hospital, Changsha, China.
1313Hepatobiliary Surgery, Henan Cancer Hospital, Zhengzhou, China.
1414Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China.
1515Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Nanning, China.
1616Department of Interventional Radiology, Cancer Center, Guangdong Provincial People's Hospital, Guangzhou, China.
1717General Surgery, Liver & Thyroid Surgery, Xiangya Hospital Central South University, Changsha, China.
1818Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
1919Medical Oncology, 900 Hospital of the Joint Logistics Support Force, Fuzhou, China.
2020Department of Integrated Chinese and Western Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
2121Hepatobiliary Surgery, The First Hospital Affiliated to AMU, Chongqing, China.
2222Digestive Department, The First Affiliated Hospital of The Fourth Military Medical University, Xi'an, China.
2323Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
2424Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
2525Interventional Department, Jiangsu Cancer Hospital, Nanjing, China.
2626Clinical Research & Development, Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China.

Tóm tắt

Abstract Purpose: We assessed the efficacy and safety of camrelizumab [an anti-programmed death (PD-1) mAb] plus apatinib (a VEGFR-2 tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods: This nonrandomized, open-label, multicenter, phase II study enrolled patients with advanced HCC who were treatment-naïve or refractory/intolerant to first-line targeted therapy. Patients received intravenous camrelizumab 200 mg (for bodyweight ≥50 kg) or 3 mg/kg (for bodyweight <50 kg) every 2 weeks plus oral apatinib 250 mg daily. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC) per RECIST v1.1. Results: Seventy patients in the first-line setting and 120 patients in the second-line setting were enrolled. As of January 10, 2020, the ORR was 34.3% [24/70; 95% confidence interval (CI), 23.3–46.6] in the first-line and 22.5% (27/120; 95% CI, 15.4–31.0) in the second-line cohort per IRC. Median progression-free survival in both cohorts was 5.7 months (95% CI, 5.4–7.4) and 5.5 months (95% CI, 3.7–5.6), respectively. The 12-month survival rate was 74.7% (95% CI, 62.5–83.5) and 68.2% (95% CI, 59.0–75.7), respectively. Grade ≥3 treatment-related adverse events (TRAE) were reported in 147 (77.4%) of 190 patients, with the most common being hypertension (34.2%). Serious TRAEs occurred in 55 (28.9%) patients. Two (1.1%) treatment-related deaths occurred. Conclusions: Camrelizumab combined with apatinib showed promising efficacy and manageable safety in patients with advanced HCC in both the first-line and second-line setting. It might represent a novel treatment option for these patients. See related commentary by Pinato et al., p. 908

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Tài liệu tham khảo

Bray, 2018, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J Clin, 68, 394, 10.3322/caac.21492

Villanueva, 2019, Hepatocellular carcinoma, N Engl J Med, 380, 1450, 10.1056/NEJMra1713263

Lin, 2019, Improved survival with radiotherapy in hepatocellular carcinoma with major vascular invasion: a propensity-matched analysis of Surveillance, Epidemiology, and End Results database, Cancer Med, 8, 515, 10.1002/cam4.1937

Balogh, 2016, Hepatocellular carcinoma: a review, J Hepatocell Carcinoma, 3, 41, 10.2147/JHC.S61146

de Martel, 2015, World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma, Hepatology, 62, 1190, 10.1002/hep.27969

Zeng, 2018, Changing cancer survival in China during 2003–15: a pooled analysis of 17 population-based cancer registries, Lancet Glob Health, 6, e555, 10.1016/S2214-109X(18)30127-X

Siegel, 2020, Cancer statistics, 2020, CA Cancer J Clin, 70, 7, 10.3322/caac.21590

El-Khoueiry, 2017, Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial, Lancet, 389, 2492, 10.1016/S0140-6736(17)31046-2

Zhu, 2018, Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial, Lancet Oncol, 19, 940, 10.1016/S1470-2045(18)30351-6

Finn, 2019, Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs. best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC), J Clin Oncol, 37, 15s, 10.1200/JCO.2019.37.15_suppl.4004

Yau, 2019, CheckMate 459: a randomized, multi-center phase III study of nivolumab (NIVO) vs. sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC), Ann Oncol, 30, v874, 10.1093/annonc/mdz394.029

Shigeta, 2020, Dual programmed death receptor-1 and vascular endothelial growth factor receptor-2 blockade promotes vascular normalization and enhances antitumor immune responses in hepatocellular carcinoma, Hepatology, 71, 1247, 10.1002/hep.30889

Finn, 2020, Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma, N Engl J Med, 382, 1894, 10.1056/NEJMoa1915745

Finn, 2020, Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma, J Clin Oncol, 38, 2960, 10.1200/JCO.20.00808

Xu, 2019, Anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: an open-label, dose escalation and expansion study, Clin Cancer Res, 25, 515, 10.1158/1078-0432.CCR-18-2484

Weber, 2016, Management of adverse events following treatment with anti-programmed death-1 agents, Oncologist, 21, 1230, 10.1634/theoncologist.2016-0055

Yau, 2019, Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): results from CheckMate 040, J Clin Oncol, 37, 4012, 10.1200/JCO.2019.37.15_suppl.4012

Li, 2020, Apatinib as second-line therapy in Chinese patients with advanced hepatocellular carcinoma: a randomized, placebo-controlled, double-blind, phase III study, J Clin Oncol, 38, 15s

Qin, 2020, Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial, Lancet Oncol, 21, 571, 10.1016/S1470-2045(20)30011-5

Wang, 2020, Reactive cutaneous capillary endothelial proliferation in advanced hepatocellular carcinoma patients treated with camrelizumab: data derived from a multicenter phase 2 trial, J Hematol Oncol, 13, 47, 10.1186/s13045-020-00886-2

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Clinical Cancer Research

Tập 27 Số 4

1003-1011

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