Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Expert Rev Anticancer Ther. 2023 Mar;23(3):279-291. doi: 10.1080/14737140.2023.2181162. Epub 2023 Feb 26.
The treatment landscape of hepatocellular carcinoma (HCC) has significantly changed over the last 5 years with multiple options in the frontline, second line, and beyond. Tyrosine kinase inhibitors (TKIs) were the first approved systemic treatments for the advanced stage of HCC; however, thanks to the increasing knowledge and characterization of the immunological features of the tumor microenvironment, the systemic treatment of HCC has been further expanded with the immune checkpoint inhibitor (ICI) approach and the following evidence of the higher efficacy obtained with combined treatment with atezolizumab plus bevacizumab over sorafenib.
In this review, we look at rationale, efficacy, and safety profiles of current and emerging ICI/TKI combination treatments and discuss the available results from other clinical trials using similar combinatorial therapeutic approaches.
Angiogenesis and immune evasion are the two key pathogenic hallmarks of HCC. While the pioneering regimen of atezolizumab/bevacizumab is consolidating as the first-line treatment of advanced HCC, it will be essential, in the near future, to determine the best second-line treatment options and how to optimize the selection of the most effective therapies. These points still need to be addressed by future studies that are largely warranted to enhance the treatment's effectiveness and ultimately to tackle down HCC lethality.
在过去的 5 年中，肝细胞癌 (HCC) 的治疗格局发生了重大变化，一线、二线及以上治疗方案有了多种选择。酪氨酸激酶抑制剂 (TKI) 是 HCC 晚期获批的首个系统治疗药物；然而，由于对肿瘤微环境免疫特征的认识不断加深和特征不断明确，免疫检查点抑制剂 (ICI) 治疗方法进一步拓展了 HCC 的系统治疗，并在联合阿替利珠单抗加贝伐珠单抗与索拉非尼治疗时获得了更高的疗效证据。
在这篇综述中，我们着眼于当前和新兴的 ICI/TKI 联合治疗的作用机制、疗效和安全性，并讨论了使用类似组合治疗方法的其他临床试验的现有结果。
血管生成和免疫逃逸是 HCC 的两个关键发病特征。虽然阿替利珠单抗/贝伐珠单抗的开创性方案已巩固为晚期 HCC 的一线治疗方法，但在不久的将来，确定最佳二线治疗方案以及如何优化选择最有效的治疗方法将至关重要。这些问题仍需要通过未来的研究来解决，这在很大程度上需要提高治疗的有效性，最终解决 HCC 的致命性问题。
