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

医学 内科学 肝细胞癌 危险系数 肿瘤科 阿替唑单抗 免疫疗法 队列 比例危险模型 荟萃分析 不利影响 癌症 置信区间 无容量
作者
Lorenz Balcar,Bernhard Scheiner,Claudia Angela Maria Fulgenzi,Antonio D’Alessio,Katharina Pomej,Marta Bofill Roig,Elias Laurin Meyer,Jaekyung Cheon,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
出处
期刊:JHEP reports [Elsevier BV]
卷期号:6 (2): 100982-100982 被引量:1
标识
DOI:10.1016/j.jhepr.2023.100982
摘要

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.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).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 upon uni- and multivariable analyses (aHR for OS and PFS: 0.79, 95% CI 0.59-1.04; 1.02, 95% CI 0.80-1.30, respectively). Objective response rates (24%/22%) and disease control rates (59%/59%) were also similar between sexes.Female phase III trial participants experienced smaller OS benefit following ICI therapy for advanced HCC, while outcomes following A+B treatment were comparable between sexes in a large real-world database. Based on the ambiguous sex-related differences in survival observed here, further investigation of sex-specific clinical and biologic determinants of responsiveness and survival following ICIs are warranted.While immune checkpoint inhibitors have emerged as standard of care for the treatment of hepatocellular carcinoma, there are conflicting reports on whether the efficacy of cancer immunotherapy differs between females and males. Our study suggests ambiguous sex-related differences in outcomes from immunotherapy in hepatocellular carcinoma. Further investigation of sex-specific clustering in clinicopathologic and immunologic determinants of responsiveness to immune checkpoint inhibitor therapy should be prioritised.PROSPERO CRD42023429625.

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