Cancer Centre of Jinling Hospital, Nanjing, China.
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Lancet Oncol. 2020 Apr;21(4):571-580. doi: 10.1016/S1470-2045(20)30011-5. Epub 2020 Feb 26.
Blocking the interaction between PD-1 and its ligands is a promising treatment strategy for advanced hepatocellular carcinoma. This study aimed to assess the antitumour activity and safety of the anti-PD-1 inhibitor camrelizumab in pretreated patients with advanced hepatocellular carcinoma.
This is a multicentre, open-label, parallel-group, randomised, phase 2 trial done at 13 study sites in China. Eligible patients were aged 18 years and older with a histological or cytological diagnosis of advanced hepatocellular carcinoma, had progressed on or were intolerant to previous systemic treatment, and had an Eastern Cooperative Oncology Group performance score of 0-1. Patients were randomly assigned (1:1) to receive camrelizumab 3 mg/kg intravenously every 2 or 3 weeks, via a centralised interactive web-response system using block randomisation (block size of four). The primary endpoints were objective response (per blinded independent central review) and 6-month overall survival, in all randomly assigned patients who had at least one dose of study treatment. Safety was analysed in all treated patients. This study is registered with ClinicalTrials.gov, number NCT02989922, and follow-up is ongoing, but enrolment is closed.
Between Nov 15, 2016, and Nov 16, 2017, 303 patients were screened for eligibility, of whom 220 eligible patients were randomly assigned and among whom 217 received camrelizumab (109 patients were given treatment every 2 weeks and 108 every 3 weeks). Median follow-up was 12·5 months (IQR 5·7-15·5). Objective response was reported in 32 (14·7%; 95% CI 10·3-20·2) of 217 patients. The overall survival probability at 6 months was 74·4% (95% CI 68·0-79·7)]. Grade 3 or 4 treatment-related adverse events occurred in 47 (22%) of 217 patients; the most common were increased aspartate aminotransferase (ten [5%]) and decreased neutrophil count (seven [3%]). Two deaths were judged by the investigators to be potentially treatment-related (one due to liver dysfunction and one due to multiple organ failure).
Camrelizumab showed antitumour activity in pretreated Chinese patients with advanced hepatocellular carcinoma, with manageable toxicities, and might represent a new treatment option for these patients.
Jiangsu Hengrui Medicine.
阻断 PD-1 与其配体的相互作用是治疗晚期肝细胞癌的一种有前途的治疗策略。本研究旨在评估抗 PD-1 抑制剂卡瑞利珠单抗在晚期肝细胞癌预处理患者中的抗肿瘤活性和安全性。
这是一项在中国 13 个研究地点进行的多中心、开放标签、平行组、随机、2 期试验。符合条件的患者年龄在 18 岁及以上，组织学或细胞学诊断为晚期肝细胞癌，先前的系统治疗进展或不耐受，东部合作肿瘤组体能状态评分为 0-1。患者通过中央交互式网络反应系统以 1:1 的比例随机分配（分组大小为 4），接受卡瑞利珠单抗 3mg/kg 静脉注射，每 2 或 3 周一次。主要终点是所有随机分配患者（至少接受一剂研究治疗）的客观缓解（经盲法独立中央审查）和 6 个月总生存率。在所有接受治疗的患者中进行安全性分析。该研究在 ClinicalTrials.gov 注册，编号为 NCT02989922，正在进行随访，但已关闭入组。
2016 年 11 月 15 日至 2017 年 11 月 16 日，对 303 名患者进行了筛选，其中 220 名符合条件的患者被随机分配，其中 217 名患者接受了卡瑞利珠单抗治疗（109 名每 2 周接受治疗，108 名每 3 周接受治疗）。中位随访时间为 12.5 个月（IQR 5.7-15.5）。217 名患者中有 32 名（14.7%；95%CI 10.3-20.2）报告了客观缓解。6 个月时的总生存率为 74.4%（95%CI 68.0-79.7）。217 名患者中有 47 名（22%）发生 3 级或 4 级与治疗相关的不良事件；最常见的是天冬氨酸氨基转移酶升高（10 例[5%]）和中性粒细胞计数降低（7 例[3%]）。两名死亡被研究者判断为可能与治疗相关（一名死于肝功能障碍，一名死于多器官衰竭）。
卡瑞利珠单抗在晚期肝细胞癌预处理的中国患者中显示出抗肿瘤活性，且毒性可耐受，可能为这些患者提供一种新的治疗选择。
江苏恒瑞医药。
