Background Immune checkpoint inhibitor (ICI)-based therapy such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab became mainstream first-line systemic treatment in advanced hepatocellular carcinoma (HCC) patients since remarkably superior efficacy of ICI-based therapy compared to tyrosine kinase inhibitors (TKIs) was reported in two recent randomized controlled trials (RCTs) (IMbrave150, HIMALAYA). However, the optimal second-line therapy after treatment failure of first-line ICI-based therapy remains unknown as no RCT has examined this issue. Summary Therefore, at present, most clinicians are empirically treating patients with TKIs or retrial of ICI or locoregional treatment (LRT) modality such as transarterial therapy, radiofrequency ablation, and radiation therapy in this clinical setting without solid evidence. In this review, we will discuss current optimal strategies for second-line treatment after the failure of first-line ICI-based therapy by reviewing published studies and ongoing prospective trials. Key Messages Clinicians should consider carefully whether to treat the patients with TKI, other ICI-based therapy, or LRT in this situation by considering several factors including liver function reserve, performance status, adverse events of previous therapy, and presence of lesion that can consider LRT such as oligoprogression and vascular invasion. In the meantime, we await the results of ongoing prospective trials to elucidate the best management options.

中文翻译：

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肝细胞癌免疫检查点抑制剂失败后的二线治疗：酪氨酸激酶抑制剂、免疫治疗重试还是局部治疗？


背景 基于免疫检查点抑制剂 (ICI) 的治疗，如 atezolizumab 加贝伐珠单抗或 durvalumab 加曲美木单抗，成为晚期肝细胞癌 (HCC) 患者的主流一线全身治疗，因为与酪氨酸激酶抑制剂 (TKI) 相比，基于 ICI 的治疗疗效显着优于）在最近的两项随机对照试验（RCT）（IMbrave150，HIMALAYA）中报告。然而，一线 ICI 治疗失败后的最佳二线治疗仍然未知，因为没有随机对照试验研究过这个问题。总结 因此，目前，大多数临床医生在临床环境中对 TKI 进行经验性治疗，或重新试验 ICI 或局部治疗 (LRT) 方式，如经动脉治疗、射频消融和放射治疗，但没有确凿的证据。在这篇综述中，我们将通过回顾已发表的研究和正在进行的前瞻性试验，讨论一线 ICI 治疗失败后当前二线治疗的最佳策略。关键信息 临床医生应仔细考虑在这种情况下是否使用 TKI、其他基于 ICI 的治疗或 LRT 治疗患者，考虑多种因素，包括肝功能储备、体能状态、既往治疗的不良事件以及可考虑的病变的存在LRT 如寡进展和血管侵犯。与此同时，我们等待正在进行的前瞻性试验的结果，以阐明最佳的管理方案。