Abstract: Regorafenib was the first drug to demonstrate a survival benefit as a second-line agent after sorafenib failure in patients with unresectable hepatocellular carcinoma (HCC). Recent studies have shown that its mechanism of action is not only limited to its very broad spectrum of inhibition of angiogenesis, tumor proliferation, spread, and metastasis, but also to its immunomodulatory properties that have favorable effects on the very intricate role that the tumor microenvironment plays in carcinogenesis and tumor growth. In this review, we discuss rationale and evidence supporting regorafenib efficacy in HCC and that led to its approval as a second-line treatment, after sorafenib failure. We also discuss the evidence from clinical practice studies that confirm the results previously achieved in clinical trials. Finally, we analyze the potential role of regorafenib in emerging combined treatment approach with immunotherapy strategies using immune checkpoint blockade and its potential extension to patient categories not included in the registrative study.

Keywords: hepatocellular carcinoma, HCC, regorafenib, tyrosine kinase inhibitor, TKI, systemic treatment, combination treatment

中文翻译：

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瑞戈非尼与其他全身疗法的结合：在肝癌中探索有前途的疗法

摘要：Regorafenib是索拉非尼治疗失败后无法手术切除的肝细胞癌（HCC）患者中作为二线药物能够生存的第一种药物。最近的研究表明，其作用机制不仅限于其对血管生成，肿瘤增殖，扩散和转移的非常广泛的抑制作用，而且还包括其免疫调节特性，这些特性对肿瘤微环境的非常复杂的作用具有良好的作用。在癌变和肿瘤生长中起作用。在这篇综述中，我们讨论了支持瑞格非尼在肝癌中的疗效的理论依据和证据，并证实了索拉非尼失败后它被批准作为二线治疗。我们还将讨论来自临床实践研究的证据，这些证据证实了先前在临床试验中获得的结果。最后，

关键词：肝细胞癌，肝癌，瑞格非尼，酪氨酸激酶抑制剂，TKI，全身治疗，联合治疗