A meta-analysis and real-world cohort study on the sex-related differences in efficacy and safety of immunotherapy for hepatocellular carcinoma

作者：Lorenz Balcar, Bernhard Scheiner, Claudia Angela Maria Fulgenzi, Antonio D’Alessio, Katharina Pomej, Marta Bofill Roig, Elias Laurin Meyer, Jaekyung Che, Naoshi Nishida, Pei‐Chang Lee, Linda Y. Wu, Celina Ang, Anja Krall, Anwaar Saeed, Bernardo Stefanini, Antonella Cammarota, Tiziana Pressiani, Yehia I. Abugabal, Shadi Chamseddine, Brooke Wietharn, Alessandro Parisi, Yi‐Hsiang Huang, Samuel Phen, Caterina Vivaldi, Francesca Salani, Gianluca Masi, Dominik Bettinger, Arndt Vogel, Johann von Felden, Kornelius Schulze, Marianna Silletta, Michael Trauner, Adel Samson, Henning Wege, Fabio Piscaglia, Peter R. Galle, Rudolf Stauber, Masatoshi Kudo, Amit G. Singal, Aleena Itani, Susanna V. Ulahannan, Neehar D. Parikh, Alessio Cortellini, Ahmed O. Kaseb, Lorenza Rimassa, Hong Jae Chon, David J. Pinato, Matthias Pinter · 发表于：JHEP Reports · 年份：2023 · DOI：10.1016/j.jhepr.2023.100982 · 被引用次数：27 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer Immunotherapy and Biomarkers、Cholangiocarcinoma and Gallbladder Cancer Studies

Background & Aims: Sex-related differences in the immune pathogenesis of hepatocellular carcinoma (HCC), particularly related to oestrogen-dependent secretion of pro-tumourigenic cytokines, are well-known. Whether sex influences the efficacy and safety of immunotherapy is not known. Methods: We performed a restricted maximum likelihood random effects meta-analysis of five phase III trials that evaluated immune checkpoint inhibitors (ICIs) in advanced HCC and reported overall survival (OS) hazard ratios (HRs) stratified by sex to evaluate sex-related differences in OS. In a real-world cohort of 840 patients with HCC from 22 centres included between 2018 and 2023, we directly compared the efficacy and safety of atezolizumab + bevacizumab (A+B) between sexes. Radiological response was reported according to RECIST v1.1. Uni- and multivariable Cox regression analyses were performed for OS and progression-free survival (PFS). Results: In the meta-analysis, immunotherapy was associated with a significant OS benefit only in male (pooled HR 0.79; 95% CI 0.73-0.86) but not in female (pooled HR 0.85; 95% CI 0.70-1.03) patients with HCC. When directly comparing model estimates, no differences in the treatment effect between sexes were observed. Among 840 patients, 677 (81%) were male (mean age 66 ± 11 years), and 163 (19%) were female (mean age 67 ± 12 years). Type and severity of adverse events were similar between the two groups. OS and PFS were comparable between males and females upo...