PDF(Pubmed)
Abstract：
Advanced hepatocellular carcinoma (HCC) is traditionally associated with limited treatment options and a poor prognosis. Sorafenib, a multiple tyrosine kinase inhibitor, was introduced in 2007 as a first-in-class systemic agent for advanced HCC. After sorafenib, a range of targeted therapies and immunotherapies have demonstrated survival benefits in the past 5 years, revolutionizing the treatment landscape of advanced HCC. More recently, evidence of novel combinations of systemic agents with distinct mechanisms has emerged. In particular, combination trials on atezolizumab plus bevacizumab and durvalumab plus tremelimumab have shown encouraging efficacy. Hence, international societies have revamped their guidelines to incorporate new recommendations for these novel systemic agents. Aside from treatment in advanced HCC, the indications for systemic therapy are expanding. For example, the combination of systemic therapeutics with locoregional therapy (trans-arterial chemoembolization or stereotactic body radiation therapy) has demonstrated promising early results in downstaging HCC. Recent trials have also explored the role of systemic therapy as neoadjuvant treatment for borderline-resectable HCC or as adjuvant treatment to reduce recurrence risk after curative resection. Despite encouraging results from clinical trials, the real-world efficacy of systemic agents in specific patient subgroups (such as patients with advanced cirrhosis, high bleeding risk, renal impairment, or cardiometabolic diseases) remains uncertain. The effect of liver disease etiology on systemic treatment efficacy warrants further research. With an increased understanding of the pathophysiological pathways and accumulation of clinical data, personalized treatment decisions will be possible, and the field of systemic treatment for HCC will continue to evolve.
摘要：
晚期肝细胞癌（HCC）传统上与有限的治疗选择和不良预后相关。索拉非尼,一种多重酪氨酸激酶抑制剂，于2007年推出，是治疗晚期肝癌的一流全身性药物。索拉非尼之后,在过去的5年中，一系列靶向疗法和免疫疗法已显示出生存益处，彻底改变了晚期肝癌的治疗前景。最近,已经出现了具有不同机制的系统性药物的新型组合的证据.特别是,阿妥珠单抗+贝伐单抗和durvalumab+tremelimumab的联合试验显示了令人鼓舞的疗效.因此，国际社会已经修改了他们的指导方针，以纳入针对这些新型系统性药物的新建议。除了治疗晚期肝癌，全身治疗的适应症正在扩大.例如,全身性治疗与局部治疗(经肝动脉化疗栓塞或立体定向放疗)相结合,在肝癌分期降低方面已显示出有希望的早期结果.最近的试验也探讨了全身治疗作为临界可切除HCC的新辅助治疗或作为辅助治疗以降低根治性切除后复发风险的作用。尽管临床试验结果令人鼓舞，全身药物在特定患者亚组(如晚期肝硬化患者，高出血风险,肾功能损害，或心脏代谢疾病)仍然不确定。肝病病因对全身治疗疗效的影响值得进一步研究。随着对病理生理途径的理解和临床数据的积累，个性化的治疗决定将是可能的，HCC的系统治疗领域将继续发展。
