临床肝胆病杂志2024，Vol.40Issue(5)：975-981,7.DOI:10.12449/JCH240517
程序性死亡受体1(PD-1)单抗联合索拉非尼或仑伐替尼治疗肝功能Child-Pugh B级不可切除肝癌患者的效果分析
Efficacy and safety of anti-PD-1 monoclonal antibody combined with sorafenib or lenvatinib in treatment of patients with Child-Pugh class B unresectable hepatocellular carcinoma
摘要
Abstract
Objective To investigate the safety and efficacy of tyrosine kinase inhibitors combined with immune checkpoint inhibitors in the treatment of patients with Child-Pugh class B unresectable hepatocellular carcinoma(uHCC).Methods A total of 96 patients with Child-Pugh class B uHCC who were admitted to Beijing Ditan Hospital,Capital Medical University,from December 31,2020 to March 30,2023 were enrolled as subjects,among whom 63 patients receiving lenvatinib combined with programmed death-1(PD-1)inhibitor were enrolled as L group and 33 patients receiving sorafenib combined with PD-1inhibitor were enrolled as S group.The primary endpoint was objective response rate(ORR),and secondary endpoints included time to progression(TTP),overall survival(OS),toxicity,drug withdrawal rate,and dose adjustment rate.The The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.Survival curves were plotted,and the Kaplan-Meier method was used to calculate the survival rate of patients in both groups,while the Log-rank test was used for comparison between the two groups.The Cox regression model was used to calculate hazard ratio(HR)and its 95%confidence interval(CI)and perform the multivariate analysis of influencing factors for prognosis.Results Among the 96 patients with uHCC,55(57.3%)had Child-Pugh class B(7 points)uHCC and 41(42.7%)had Child-Pugh class B(8—9 points)uHCC.The L group had a significantly higher ORR than the S group(46.0%vs 15.2%,P=0.003),and there were no significant differences between the L group and the S group in median TTP(6.6 months vs 3.5 months,P=0.48)or OS(13.8 months vs 13.2 months,P=0.95).There was no significant difference in median TTP between the patients with Child-Pugh class B(7 points)uHCC and those with Child-Pugh class B(8—9 points)uHCC(6.6 months vs 4.8 months,P=0.35),while there was a significant difference in OS between these two groups of patients(14.5 months vs 8.8 months,P=0.045).The multivariate analysis showed that ORR was a protective factor for both TTP(HR=0.18,95%CI:0.09—0.36,P<0.001)and OS(HR=0.20,95%CI:0.09—0.43,P<0.001).There were no significant differences between the L group and the S group in the overall incidence rate of adverse reactions(98.4%vs 97.0%)and the incidence rate of grade≥3 adverse reactions(68.3%vs 63.6%),and there were also no significant differences between the two groups in dose adjustment rate(84.8%vs 70.2%)and drug withdrawal rate(56.1%vs 72.7%).Conclusion Compared with the regimen of sorafenib combined with PD-1 inhibitor,the regimen of lenvatinib combined with PD-1 inhibitor can improve the ORR of patients with Child-Pugh class B uHCC,with similar prognosis and safety profile between the two groups.关键词
癌,肝细胞/肝功能不全/索拉非尼/仑伐替尼/免疫检查点抑制剂/治疗结果Key words
Carcinoma,Hepatocellular/Hepatic Insufficiency/Sorafenib/Lenvatinib/Immune Checkpoint Inhibitors/Treatment Outcome引用本文复制引用
孙巍,丁晓燕,陈京龙..程序性死亡受体1(PD-1)单抗联合索拉非尼或仑伐替尼治疗肝功能Child-Pugh B级不可切除肝癌患者的效果分析[J].临床肝胆病杂志,2024,40(5):975-981,7.基金项目
首都卫生发展科研专项(首发2022-2-2175) Capital Health Development Research Project(2022-2-2175) （首发2022-2-2175）
