晚期肝细胞癌一线系统治疗药物有效性和安全性的网络荟萃分析

Efficacy and safety of first-line systemic therapies for advanced hepatocellular carcinoma:A system review and network meta-analysis

目的比较晚期肝细胞癌一线系统治疗药物的有效性和安全性,供临床实践作参考。方法网络检索PubMed、Cochrane Library、Embase和Web of Science等文献数据库,检索时限均为建库至2021年6月,根据预设的纳入标准筛选文献进行网络荟萃分析。结果共纳入12项随机对照研究,合计8058例患者。网络荟萃分析结果显示,相较于索拉非尼,信迪利单抗联合贝伐珠单抗生物类似物(IBI305)、阿替利珠单抗联合贝伐珠单抗和多纳非尼均降低了患者的死亡风险(HR=0.57,95%CI:0.43~0.75;HR=0.58,95%CI:0.42~0.80;HR=0.83,95%CI:0.70~0.99),该3种治疗方式有最高的P-score值,分别为0.956、0.948和0.764;在有或无“大血管侵犯/肝外转移”的两组患者亚组中,3种治疗方案的排名类似;安全性方面,除安慰剂之外,多纳非尼因不良事件终止研究治疗、减量研究药物和暂停研究治疗的P-score值均位居首位。结论晚期肝细胞癌一线系统治疗药物中,信迪利单抗联合贝伐珠单抗生物类似物、阿替利珠单抗联合贝伐珠单抗和多纳非尼单药治疗均可显著改善晚期肝细胞癌患者的总生存时间;而多纳非尼的安全性和耐受性更佳。

Objective To compare the efficacy and safety of current domestic and foreign first-line systemic therapies of advanced hepatocellular carcinoma,so as to provide reference for clinical practice.Methods The mainstream electronic literature database including PubMed,Cochrane library,Embase and Web of Science was searched up to June 2021,and eligible studies were identified for network meta-analysis.Results A total of 8058 patients from 12 eligible randomized controlled studies were included in this analysis.Compared with sorafenib,sintilimab plus bevacizumab biosimilar(IBI305),atezolizumab plus bevacizumab and donafenib obviously reduced the risk of death(HR=0.57,95%CI:0.43-0.75;HR=0.58,95%CI:0.42-0.80;HR=0.83,95%CI:0.70-0.99).The highest P-score for them were 0.956,0.948 and 0.764,respectively.The ranking of those three treatments was similar in the subgroup of patients with or without macrovascular invasion/extrahepatic metastasis.In terms of safety,except for placebo control,the P-score of donafenib for termination of study treatment,reduction of study drugs and interruption of study treatment due to adverse events ranked the first position.Conclusion Among the current domestic and foreign first-line treatments for advanced hepatocellular carcinoma,the combined therapy of sintilimab plus bevacizumab biosimilar,atezolizumab plus bevacizumab and donafenib monotherapy can improve the overall survival of patients.But donafenib also has showed much better safety and tolerability.