Immune Checkpoint Inhibitors for Child-Pugh Class B Advanced Hepatocellular Carcinoma
Authors: 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 
Published: August 2023

ImportanceImmune 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.ObjectiveTo 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.Data SourcesPubMed, Embase, Web of Science, and Cochrane Library were searched for relevant studies from inception through June 15, 2022.Study SelectionRandomized 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.Data Extraction and SynthesisThe 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 &amp;gt; 50%); otherwise, a fixed-effect model was used.Main Outcomes and MeasuresThe 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.ResultsA 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 &amp;lt; .001) and DCR (odds ratio, 0.64; 95% CI, 0.50-0.81; P &amp;lt; .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.Conclusions and RelevanceThe 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.