Since sorafenib was established as the standard of care for patients with advanced hepatocellular carcinoma, various tyrosine kinase inhibitors, targeting vascular endothelial growth factor receptor and other molecular growth factors, have been developed. Lenvatinib demonstrated non-inferiority to sorafenib in terms of the overall survival, and it has also become confirmed as another standard of care for patients with advanced hepatocellular carcinoma. Recently, various immune checkpoint inhibitors have been investigated, either as monotherapy or in combination with another agent, and superiority of the combination of atezolizumab plus bevacizumab, in terms of the overall survival and progression-free survival, has been demonstrated over sorafenib, which is recognized as the treatment regimen of first choice for first-line systemic therapy of advanced hepatocellular carcinoma. Regorafenib, cabozantinib and ramucirumab have been demonstrated to show survival benefits as second-line treatment agents for progressive disease after first-line sorafenib treatment. There are still various medical requirements in systemic therapy for hepatocellular carcinoma. To date, no evidence has been established for the selection of sequential treatment after immune checkpoint inhibitor-containing treatments, especially atezolizumab plus bevacizumab. A promising treatment for Child-Pugh class B hepatocellular carcinoma patients is also an urgent medical need that has not yet been met. Although there are some difficulties in establishing the needed evidence, well-designed clinical trials are warranted.

中文翻译：

---

肝细胞癌的全身治疗：现状和未来展望

自从索拉非尼被确立为晚期肝细胞癌患者的护理标准以来，各种酪氨酸激酶抑制剂，靶向血管内皮生长因子受体和其他分子生长因子，已经被开发出来。乐伐替尼在总生存率方面不劣于索拉非尼，也被证实为晚期肝细胞癌患者的另一种护理标准。最近，已经研究了各种免疫检查点抑制剂，无论是作为单一疗法还是与另一种药物联合使用，并且在总生存期和无进展生存期方面，阿特珠单抗联合贝伐珠单抗的优势已被证明优于索拉非尼，被公认为晚期肝细胞癌一线全身治疗的首选治疗方案。瑞戈非尼、卡博替尼和雷莫芦单抗已被证明作为一线索拉非尼治疗后进展性疾病的二线治疗药物显示出生存获益。肝细胞癌的全身治疗仍有各种医学要求。迄今为止，尚无证据表明在包含免疫检查点抑制剂的治疗后选择序贯治疗，尤其是 atezolizumab 加贝伐珠单抗。Child-Pugh B 级肝细胞癌患者的有希望的治疗方法也是尚未满足的紧迫医疗需求。尽管在建立所需证据方面存在一些困难，但设计良好的临床试验是有必要的。