临床肝胆病杂志2024，Vol.40Issue(10) ：2034-2041.DOI:10.12449/JCH241017

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

成龙 张悦 刘毓屾 杜肇清 郭朝阳 樊扬威 李婷 高旭 谢恩睿 邢梓轩 武文华 吴胤瑛 杨明博 李婕 张煜 康文 王文俊 纪泛扑 郭江 高宁
临床肝胆病杂志2024，Vol.40Issue(10) ：2034-2041.DOI:10.12449/JCH241017
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  • NSTL
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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

成龙 1张悦 2刘毓屾 3杜肇清 4郭朝阳 5樊扬威 6李婷 7高旭 8谢恩睿 9邢梓轩 9武文华 9吴胤瑛 6杨明博 10李婕 11张煜 4康文 3王文俊 9纪泛扑 9郭江 1高宁9
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作者信息

  • 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;西安市第八医院肝病四科,西安 710061
  • 3. 空军军医大学第二附属医院感染科,西安 710038
  • 4. 陕西省人民医院肝胆外科,西安 710068
  • 5. 山东省立医院感染科,济南 250021
  • 6. 西安交通大学第一附属医院肿瘤科,西安 710061
  • 7. 西安交通大学第二附属医院感染科,西安 710004;咸阳市第一人民医院血液风湿免疫科,陕西 咸阳 721000
  • 8. 西安交通大学第二附属医院感染科,西安 710004;西安交通大学第二附属医院消化科,西安 710004
  • 9. 西安交通大学第二附属医院感染科,西安 710004
  • 10. 西安市第八医院肝病四科,西安 710061
  • 11. 南京鼓楼医院感染科,南京 210008
  • 折叠

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(irAE)发生情况.计数资料两组间比较采用χ2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irAE和3/4级irAE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irAE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.

Abstract

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted 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 factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

关键词

癌,肝细胞/抗体,单克隆,人/分子靶向治疗/老年人

Key words

Carcinoma,Hepatocellular/Antibodies,Monoclonal,Humanized/Molecular Targeted Therapy/Aged

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基金项目

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)

出版年

2024
临床肝胆病杂志
吉林大学

临床肝胆病杂志

CSTPCD北大核心
影响因子：1.428
ISSN：1001-5256
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