Xie Enrui, Yeo Yee Hui, Scheiner Bernhard, Zhang Yue, Hiraoka Atsushi, Tantai Xinxing, Fessas Petros, de Castro Tiago, D'Alessio Antonio, Fulgenzi Claudia Angela Maria, Xu Shuo, Tsai Hong-Ming, Kambhampati Swetha, Wang Wenjun, Keenan Bridget P, Gao Xu, Xing Zixuan, Pinter Matthias, Lin Yih-Jyh, Guo Zhanjun, Vogel Arndt, Tanaka Takaaki, Kuo Hsin-Yu, Kelley Robin K, Kudo Masatoshi, Yang Ju Dong, Pinato David J, Ji Fanpu
Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California.
JAMA Oncol. 2023 Oct 1;9(10):1423-1431. doi: 10.1001/jamaoncol.2023.3284.
Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced hepatocellular carcinoma (HCC). However, data on ICI therapy in patients with advanced HCC and impaired liver function are scarce.
To conduct a systematic review and meta-analysis to determine the efficacy and safety of ICI treatment for advanced HCC with Child-Pugh B liver function.
PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant studies from inception through June 15, 2022.
Randomized clinical trials, cohort studies, or single-group studies that investigated the efficacy or safety of ICI therapy for Child-Pugh B advanced HCC were included.
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline was followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 > 50%); otherwise, a fixed-effect model was used.
The objective response rate (ORR) and overall survival (OS) were considered to be the primary efficacy outcomes of ICI treatment for Child-Pugh B advanced HCC, and the incidence of treatment-related adverse events (trAEs) was set as the primary measure for the safety outcome.
A total of 22 studies including 699 patients with Child-Pugh B and 2114 with Child-Pugh A advanced HCC comprised the analytic sample (median age range, 53-73 years). Upon pooled analysis, patients treated with ICIs in the Child-Pugh B group had an ORR of 14% (95% CI, 11%-17%) and disease control rate (DCR) of 46% (95% CI, 36%-56%), with a median OS of 5.49 (95% CI, 3.57-7.42) months and median progression-free survival of 2.68 (95% CI, 1.85-3.52) months. The rate of any grade trAEs in the Child-Pugh B group was 40% (95% CI, 34%-47%) and of grade 3 or higher trAEs was 12% (95% CI, 6%-23%). Compared with the Child-Pugh A group, the ORR (odds ratio, 0.59; 95% CI, 0.43-0.81; P < .001) and DCR (odds ratio, 0.64; 95% CI, 0.50-0.81; P < .001) were lower in the Child-Pugh B group. Child-Pugh B was independently associated with worse OS in patients with advanced HCC treated with ICIs (hazard ratio, 2.72 [95% CI, 2.34-3.16]; adjusted hazard ratio, 2.33 [95% CI, 1.81-2.99]). However, ICIs were not associated with increased trAEs in the Child-Pugh B group.
The findings of this systematic review and meta-analysis suggest that although the safety of ICI treatment was comparable between patients with HCC with vs without advanced liver disease and the treatment resulted in a significant number of radiologic responses, survival outcomes are still inferior in patients with worse liver function. More study is needed to determine the effectiveness of ICI treatment in this population.
免疫检查点抑制剂（ICI）越来越多地用于晚期肝细胞癌（HCC）患者。然而，关于晚期HCC且肝功能受损患者接受ICI治疗的数据却很匮乏。
进行一项系统评价和荟萃分析，以确定ICI治疗对肝功能为Child-Pugh B级的晚期HCC的疗效和安全性。
检索了PubMed、Embase、Web of Science和Cochrane图书馆，以获取从创刊至2022年6月15日的相关研究。
纳入调查ICI治疗对Child-Pugh B级晚期HCC疗效或安全性的随机临床试验、队列研究或单组研究。
遵循系统评价和荟萃分析的首选报告项目指南来提取数据。如果异质性显著（I2>50%），则采用随机效应模型；否则，使用固定效应模型。
客观缓解率（ORR）和总生存期（OS）被视为ICI治疗Child-Pugh B级晚期HCC的主要疗效结局，治疗相关不良事件（trAE）的发生率被设定为安全性结局的主要衡量指标。
共有22项研究纳入分析样本，其中包括699例肝功能为Child-Pugh B级的患者和2114例肝功能为Child-Pugh A级的晚期HCC患者（中位年龄范围为53 - 73岁）。经汇总分析，Child-Pugh B组接受ICI治疗的患者ORR为14%（95%CI，11% - 17%），疾病控制率（DCR）为46%（95%CI，36% - 56%），中位OS为5.49个月（95%CI，3.57 - 7.42），中位无进展生存期为2.68个月（95%CI，1.85 - 3.52）。Child-Pugh B组任何级别trAE的发生率为40%（95%CI，34% - 47%），3级或更高级别trAE的发生率为12%（95%CI，6% - 23%）。与Child-Pugh A组相比，Child-Pugh B组的ORR（比值比，0.59；95%CI，0.43 - 0.81；P <.001）和DCR（比值比，0.64；95%CI，0.50 - 0.81；P <.001）较低。Child-Pugh B级独立与接受ICI治疗的晚期HCC患者较差的OS相关（风险比，2.72 [95%CI，2.34 - 3.16]；调整后风险比，2.33 [95%CI，1.81 - 2.99]）。然而，ICI与Child-Pugh B组trAE增加无关。
这项系统评价和荟萃分析的结果表明，尽管晚期肝病和非晚期肝病的HCC患者接受ICI治疗的安全性相当，且该治疗产生了大量影像学缓解，但肝功能较差患者的生存结局仍然较差。需要更多研究来确定ICI治疗在该人群中的有效性。
