替雷利珠单抗治疗既往接受过治疗的晚期肝细胞癌患者（RATIONALE-208）：一项多中心、非随机、开放标签的2期试验。
Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial.
作者信息
Ren Zhenggang, Ducreux Michel, Abou-Alfa Ghassan K, Merle Philippe, Fang Weijia, Edeline Julien, Li Zhiwei, Wu Lihua, Assenat Eric, Hu Sheng, Rimassa Lorenza, Zhang Tao, Blanc Jean-Frédéric, Pan Hongming, Ross Paul, Yen Chia-Jui, Tran Albert, Shao Guoliang, Bouattour Mohamed, Chen Yajin, Meyer Tim, Hou Jinlin, Tougeron David, Bai Yuxian, Hou Ming-Mo, Meng Zhiqiang, Wu John, Li Vincent, Chica-Duque Sandra, Cheng Ann-Lii
机构信息
Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
Medical Oncology Department, Gustave Roussy, INSERM U1279, Paris-Saclay University, Villejuif, France.
出版信息
Liver Cancer. 2022 Oct 4;12(1):72-84. doi: 10.1159/000527175. eCollection 2023 Feb.
INTRODUCTION
Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC.
METHODS
The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab.
RESULTS
Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% ( = 32/249; 95% confidence interval [CI], 9-18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8-20]; two or more prior lines, 13% [95% CI, 7-20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment.
CONCLUSION
Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.
引言
替雷利珠单抗（抗程序性细胞死亡蛋白1抗体）在包括肝细胞癌（HCC）在内的晚期实体瘤患者中显示出初步的抗肿瘤活性和耐受性。本研究旨在评估替雷利珠单抗在先前接受过治疗的晚期HCC患者中的疗效和安全性。
方法
多区域2期研究RATIONALE-208考察了替雷利珠单抗单药治疗（每3周静脉注射200mg）用于Child-Pugh A级、巴塞罗那临床肝癌分期为B或C期且接受过一种或多种先前全身治疗线数的晚期HCC患者。主要终点为客观缓解率（ORR），由独立评审委员会根据实体瘤疗效评价标准第1.1版进行影像学确认。对接受≥1剂替雷利珠单抗的患者进行安全性评估。
结果
在2018年4月9日至2019年2月27日期间，249例符合条件的患者入组并接受治疗。经过中位12.7个月的研究随访，ORR为13%（n = 32/249；95%置信区间[CI]，9%-18%），包括5例完全缓解和27例部分缓解。先前治疗线数不影响ORR（一线治疗，13%[95%CI，8%-20%]；两线或更多线治疗，13%[95%CI，7%-20%]）。中位缓解持续时间未达到。疾病控制率为53%，中位总生存期为13.2个月。在249例患者中，38例（15%）患者报告了≥3级治疗相关不良事件；最常见的是10例（4%）患者出现肝转氨酶升高。治疗相关不良事件导致13例（5%）患者停药或46例（19%）患者延迟给药。根据研究者评估，无死亡归因于治疗。
结论
替雷利珠单抗在先前接受过治疗的晚期HCC患者中显示出持久的客观缓解，无论先前治疗线数如何，且耐受性可接受。
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