卡瑞利珠单抗联合分子靶向药物治疗老年晚期肝细胞癌患者的效果和安全性分析  

Efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with advanced hepatocellular carcinoma

作　　者：成龙 张悦 刘毓屾 杜肇清 郭朝阳 樊扬威 李婷[2,9] 高旭 谢恩睿 邢梓轩 武文华 吴胤瑛[8] 杨明博 李婕 张煜 康文[5] 王文俊 纪泛扑 郭江[1] 高宁 CHENG Long;ZHANG Yue;LIU Yushen;DU Zhaoqing;GUO Zhaoyang;FAN Yangwei;LI Ting;GAO Xu;XIE Enrui;XING Zixuan;WU Wenhua;WU Yinying;YANG Mingbo;LI Jie;ZHANG Yu;KANG Wen;WANG Wenjun;JI Fanpu;GUO Jiang;GAO Ning(Department of Oncology and Interventional Radiology,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China;Department of Infectious Diseases,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China;Department of Gastroenterology,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China;Fourth Department of Liver Diseases,Xi’an Eighth Hospital,Xi’an 710061,China;Department of Infectious Diseases,The Second Affiliated Hospital of Air Force Medical University,Xi’an 710038,China;Department of Hepatobiliary Surgery,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;Department of Infectious Diseases,Shandong Provincial Hospital,Jinan 250021,China;Department of Medical Oncology,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China;Department of Hematology,Rheumatology and Immunology,The First People’s Hospital of Xianyang,Xianyang,Shaanxi 721000,China;Department of Infectious Diseases,Nanjing Drum Tower Hospital,Nanjing 210008,China)

机构地区：[1]首都医科大学附属北京地坛医院肿瘤介入科,北京100015 [2]西安交通大学第二附属医院感染科,西安710004 [3]西安交通大学第二附属医院消化科,西安710004 [4]西安市第八医院肝病四科,西安710061 [5]空军军医大学第二附属医院感染科,西安710038 [6]陕西省人民医院肝胆外科,西安710068 [7]山东省立医院感染科,济南250021 [8]西安交通大学第一附属医院肿瘤科,西安710061 [9]咸阳市第一人民医院血液风湿免疫科,陕西咸阳721000 [10]南京鼓楼医院感染科,南京210008

出　　处：《临床肝胆病杂志》2024年第10期2034-2041,共8页Journal of Clinical Hepatology

基　　金：国家自然科学基金(82170626);陕西省自然科学基金(2022SF-451);首都卫生发展科研专项(首发2024-2-2176)。

摘　　要：目的探究老年不可切除/晚期肝细胞癌(HCC)患者使用卡瑞利珠单抗联合分子靶向药物的效果并评估使用过程中的安全情况。方法回顾性纳入了2019年1月1日—2021年3月31日就诊于6家医院的不可切除/晚期HCC患者,所有患者接受卡瑞利珠单抗治疗,84.8%的患者同时联合了靶向治疗,根据患者年龄分为老年组(≥65岁)及非老年组(<65岁),评估两组患者总生存期(OS)、无进展生存期(PFS)、客观缓解率(ORR)、疾病控制率(DCR)和免疫相关不良反应(ir AE)发生情况。计数资料两组间比较采用χ^(2)检验或Fisher确切检验,符合正态分布的计量资料两组间比较采用成组t检验,非正态分布的计量资料两组间比较采用Mann-Whitney U检验。生存分析采用Kaplan-Meier法,生存曲线差异比较采用Log-rank检验。采用单因素和多因素Cox比例风险回归分析确定6个月PFS和DCR的独立影响因素。结果共纳入99例患者,其中老年组27例,非老年组72例。老年组12个月总生存率、ORR和DCR分别为67.8%、44.4%和74.1%,中位PFS为6.4(3.0~12.4)个月,与非老年组患者比较差异均无统计学意义(P值均>0.05)。老年组的中位OS尚未达到,非老年组中位OS为18.9(13.0~24.8)个月,两组比较差异无统计学意义(P=0.485)。单因素及多因素Cox回归分析显示,基线大血管浸润(MVI)是6个月PFS(HR=2.603,95%CI:1.136~5.964,P=0.024)和DCR(HR=3.963,95%CI:1.671~9.397,P=0.002)的独立危险因素,而年龄、性别、HBV感染病因、出现肝外转移、Child-Pugh B级和AFP>400 ng/mL与6个月PFS和DCR无关。老年组患者中任何级别的ir AE和3/4级ir AE发生率分别为51.9%和25.9%,与非老年组患者比较差异均无统计学意义(P值均>0.05);两组最常见的ir AE为皮肤疾病(39.4%)。结论卡瑞利珠单抗联合分子靶向药物治疗≥65岁不可切除/晚期HCC患者的效果和安全性与<65岁患者相当。MVI与免疫治疗应答不佳和不良预后相关。Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with moleculartargeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(<65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0—12.4)months,with no significant differences compared with the non-elderly group(all P>0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0—24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk fact

关 键 词：癌 肝细胞 抗体 单克隆 人 分子靶向治疗 老年人 

分 类 号：R735.7[医药卫生—肿瘤]