Juravinski Cancer Centre, McMaster University, 699 Concession St, Hamilton, ON L8V 5C2, Canada.
Princess Margaret Cancer Centre, University of Toronto, 610 University Ave, Toronto, ON M5G 2C4, Canada.
Cancer Treat Rev. 2023 Jul;118:102584. doi: 10.1016/j.ctrv.2023.102584. Epub 2023 May 27.
Since approval of sorafenib in 2008, systemic therapy has been established as the main treatment option for advanced hepatocellular carcinoma (HCC). Recently, immune checkpoints inhibitors (ICIs) have been extensively tested in this setting. Multiple ICI combination regimens have recently received regulatory approval and new data continues to emerge. The purpose of this review is to provide a comprehensive summary of the most up-to-date evidence on ICI combinations in advanced HCC.
A search of published and presented literature was conducted to identify phase III trials of ICI combinations in advanced HCC patients. Supplemental bibliographic search of review articles and meta-analyses was also conducted. Efficacy and safety data was summarized in text, tables, and plots.
The literature search identified a total of six phase III trials assessing ICI combinations in advanced HCC. Two trials compared ICI plus anti-VEGF monoclonal antibody combinations to sorafenib, three trials compared ICI plus tyrosine kinase inhibitor (TKI) combinations to TKIs alone, and one trial compared a dual ICI regimen to sorafenib. Statistically significant survival benefits were seen with atezolizumab-bevacizumab and sintilimab-bevacizumab biosimilar as well as durvalumab-tremelimumab and camrelizumab-rivoceranib combinations. ICI combination regimens have also shown improvements in response rates and progression-free survival relative to the previous standard of care, sorafenib, and generally presented predictable and manageable safety profiles.
ICI combinations represent the new standard of care for advanced HCC. Ongoing randomized trials and real-world evidence will further clarify the role of these combinations in this rapidly evolving field.
自 2008 年索拉非尼获批以来，系统治疗已成为晚期肝细胞癌（HCC）的主要治疗选择。最近，免疫检查点抑制剂（ICI）在该领域得到了广泛的测试。最近，多种 ICI 联合方案已获得监管批准，新数据不断涌现。本综述的目的是提供晚期 HCC 中 ICI 联合治疗的最新证据的综合总结。
对已发表和已发表的文献进行了检索，以确定晚期 HCC 患者中 ICI 联合治疗的 III 期试验。还对综述文章和荟萃分析的补充文献进行了检索。疗效和安全性数据以文字、表格和图表的形式进行了总结。
文献检索共确定了六项评估晚期 HCC 中 ICI 联合治疗的 III 期试验。两项试验比较了 ICI 联合抗血管内皮生长因子（VEGF）单克隆抗体与索拉非尼的疗效，三项试验比较了 ICI 联合酪氨酸激酶抑制剂（TKI）与 TKI 单药的疗效，一项试验比较了双重 ICI 方案与索拉非尼的疗效。阿替利珠单抗-贝伐单抗和信迪利单抗-贝伐珠单抗生物类似物以及度伐利尤单抗-替西利木单抗和卡瑞利珠单抗-瑞戈非尼联合治疗均显示出具有统计学意义的生存获益。ICI 联合治疗方案与之前的标准治疗药物索拉非尼相比，也显示出了在缓解率和无进展生存期方面的改善，并且通常表现出可预测和可管理的安全性特征。
ICI 联合治疗代表了晚期 HCC 的新标准。正在进行的随机试验和真实世界证据将进一步阐明这些联合方案在这一快速发展领域中的作用。
