摘要
目的分析在载药栓塞微球经肝动脉化疗栓塞术(DTACE)联合阿帕替尼治疗不可切除肝癌后,二线追加卡瑞利珠单抗的安全性和有效性。方法回顾性分析2019年12月—2020年12月于郑州大学第一附属医院就诊的89例二线追加卡瑞利珠单抗的肝癌患者资料。主要观察终点是使用卡瑞利珠单抗后总生存期(OS)和无进展生存期(PFS),次要终点包括客观缓解率(ORR)、疾病控制率(DCR)和治疗相关不良事件(TRAE)。采用Kaplan-Meier法估算生存曲线,基线特征亚组分层分析采用Log-rank检验进行比较,分析影响患者预后的相关因素。结果本研究共筛选并随访了89例患者。随访至2021年12月,中位随访时间为16个月,中位OS为17.0(95%CI:15.3~18.7)个月,中位PFS为7.0(95%CI:6.2~7.8)个月。不同ECOG-PS、肝功能Child-Pugh分级、门静脉侵犯、进展模式、DTACE次数、口服阿帕替尼时长和应用卡瑞利珠单抗时长的患者OS及PFS之间差异具有统计学意义(P值均<0.05)。应用卡瑞利珠单抗后3个月与6个月ORR分别为39.3%和22.4%,DCR分别为80.9%和54.1%。Log-rank检验单因素分析结果表明:DTACE次数为3~4、1~2比0次的患者显著改善中位OS[22.0(95%CI:21.1~22.9)个月vs 17.0(95%CI:15.8~18.2)个月vs 10.0(95%CI:7.0~13.0)个月,χ^(2)=31.423,P<0.001]与PFS[10.0(95%CI:7.0~13.0)个月vs 7.0(95%CI:6.2~7.8)个月vs 3.0(95%CI:1.9~4.1)个月,χ^(2)=20.741,P<0.001];阿帕替尼应用时长>4个月比≤4个月的患者显著改善中位OS[21.0(95%CI:19.1~22.9)个月vs 14.0(95%CI:10.4~17.6)个月,χ^(2)=19.399,P<0.001]与PFS[9.0(95%CI:7.3~10.7)个月vs 5.0(95%CI:4.0~6.0)个月,χ^(2)=27.733,P<0.001];卡瑞利珠单抗应用时长>5个月比≤5个月的患者显著改善中位OS[22.0(95%CI:20.2~23.8)个月vs 13.0(95%CI:9.3~16.7)个月,χ^(2)=22.336,P<0.001]与PFS[9.0(95%CI:7.0~11.0)个月vs 5.0(95%CI:4.1~5.9)个月,χ^(2)=26.141,P<0.001]。DTACE术后不良事件为栓塞后综合征,给予对症处理后缓解。靶向药物和免疫治疗相关不良反应经对症支持治疗后均缓解,无4级及以上不良反应,无患者因TRAE而停用靶免治疗。结论DTACE联合阿帕替尼治疗不可切除肝癌进展后追加卡瑞利珠单抗疗效确切,TRAE总体安全可控。
Objective To investigate the safety and efficacy of camrelizumab added to second-line therapy after drug- eluting bead transarterial chemoembolization(DTACE)combined with apatinib for unresectable hepatocellular carcinoma (HCC).Methods A retrospective analysis was performed for 89 HCC patients with camrelizumab added to second-line therapy who attended The First Affiliated Hospital of Zhengzhou University from December 2019 to December 2020.The primary endpoints were overall survival(OS)and progression-free survival(PFS)after the application of camrelizumab,and the secondary endpoints were objective remission rate(ORR),disease control rate(DCR),and treatment-related adverse events(TRAEs).The Kaplan-Meier method was used to plot survival curves,the Log-rank test was used for stratified analysis of subgroups based on baseline characteristics,and the influencing factors for prognosis were analyzed.Results A total of 89 patients were screened and followed up in this study.The patients were followed up to December 2021,with a median follow-up time of 16 months,a median OS time of 17.0(95%confidence interval[CI]:15.3-18.7)months,and a median PFS time of 7.0(95%CI:6.2-7.8)months.There were significant differences in OS and PFS between the patients with different ECOG-PS scores,liver function Child-Pugh classes,portal vein invasion,patterns of progression,times of DTACE treatment,durations of oral administration of apatinib,and durations of application of camrelizumab(all P<0.05).At 3 and 6 months after the application of camrelizumab,ORR was 39.3%and 22.4%,respectively,and DCR was 80.9%and 54.1%,respectively.The univariate analysis using the Log-rank test showed that compared with the patients receiving 0 time of DTACE treatment,the patients receiving 3-4 or 1-2 times of DTACE treatment had significant improvements in median OS[22.0(95%CI:21.1-22.9)months and 17.0(95%CI:15.8-18.2)months vs 10.0(95%CI:7.0-13.0)months,χ^(2)=31.423,P<0.001]and PFS[10.0(95%CI:7.0-13.0)months and 7.0(95%CI:6.2-7.8)months vs 3.0(95%CI:1.9-4.1)months,χ^(2)=20.741,P<0.001];compared with the patients using apatinib for≤4 months,the patients using apatinib for>4 months had significant improvements in median OS[21.0(95%CI:19.1-22.9)months vs 14.0(95%CI:10.4-17.6)months,χ^(2)=19.399,P<0.001]and PFS[9.0(95%CI:7.3-10.7)months vs 5.0(95%CI:4.0-6.0)months,χ^(2)=27.733,P<0.001];compared with the patients using camrelizumab for≤5 months,the patients using camrelizumab for>5 months had significant improvements in median OS[22.0(95%CI:20.2-23.8)months vs 13.0(95%CI:9.3-16.7)months,χ^(2)=22.336,P<0.001]and PFS[9.0(95%CI:7.0-11.0)months vs 5.0(95%CI:4.1-5.9)months,χ^(2)=26.141,P<0.001].Post-embolization syndrome was the adverse event after DTACE and resolved after symptomatic treatment.Adverse reactions related to targeted drugs and immunotherapy all resolved after symptomatic supportive treatment,with no grade≥4 adverse reactions,and no patients withdrew from target-free therapy due to TRAEs.Conclusion As for DTACE combined with apatinib in the treatment of unresectable HCC,camrelizumab added after progression has a marked therapeutic efficacy with safe and controllable TRAEs.
作者
张延藏
王满周
韩新巍
段旭华
任建庄
李浩
王文辉
许文泽
ZHANG Yancang;WANG Manzhou;HAN Xinwei;DUAN Xuhua;REN Jianzhuang;LI Hao;WANG Wenhui;XU Wenze(Department of Interventional Radiology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)
出处
《临床肝胆病杂志》
CAS
北大核心
2023年第4期834-842,共9页
Journal of Clinical Hepatology
基金
2021年河南省医学科技攻关省部共建重大项目(SBGJ202102100)。
