仑伐替尼联合程序性死亡受体-1抗体治疗不可切除或进展期肝细胞癌的临床疗效  

Clinical efficacy of combination therapy with lenvatinib and programmed death-1 antibodies in unresectable or advanced hepatocellular carcinoma

作　　者：徐彬 朱小东 黄成 沈英皓 诸金金 李美龄 刘洁 周俭 樊嘉 孙惠川 Xu Bin;Zhu Xiaodong;Huang Cheng;Shen Yinghao;Zhu Jinjin;Li Meiling;Liu Jie;Zhou Jian;Fan Jia;Sun Huichuan(Department of Liver Surgery,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院肝肿瘤外科,上海200032

出　　处：《中华消化外科杂志》2021年第2期197-204,共8页Chinese Journal of Digestive Surgery

基　　金：国家重点基础研究发展规划(973计划)项目(2015CB554005);国家自然科学基金(81672326,81871928,81871929);上海市优秀学术/技术带头人计划(17XD1401100)。

摘　　要：目的探讨仑伐替尼联合程序性死亡受体-1(PD-1)抗体治疗不可切除或进展期肝细胞癌(以下简称肝癌)的临床疗效。方法采用回顾性描述性研究方法。收集2018年9月至2020年1月复旦大学附属中山医院收治的59例不可切除或进展期肝癌病人的临床病理资料;男54例,女5例;中位年龄为52岁,年龄范围为25~73岁。59例病人均采用仑伐替尼联合PD-1抗体治疗,其中43例直接进行一线治疗,16例因仑伐替尼或索拉非尼单药治疗发生肿瘤进展或不耐受后进行二线治疗。观察指标:(1)临床疗效。(2)药物不良反应及治疗情况。(3)随访及生存情况。采用门诊和电话方式进行随访,了解病人靶病灶肿瘤长径、总体生存和疾病无进展生存情况。随访时间截至2020年12月。偏态分布的计量资料以M(P25,P75)或M(范围)表示。计数资料以绝对数和(或)百分比表示。采用Kaplan-Meier法计算中位缓解持续时间、中位总体生存时间、中位疾病无进展生存时间和生存率并绘制生存曲线。结果(1)临床疗效:59例肝癌病人治疗后客观缓解率、完全缓解率、部分缓解率、疾病稳定率、疾病进展率、治疗起效时间、中位缓解持续时间分别为37.3%(22/59)、11.9%(7/59)、25.4%(15/59)、37.3%(22/59)、25.4%(15/59)、2.6个月(2.1个月,4.0个月)、6.3个月[95%可信区间(CI)为2.2~10.5个月]。43例进行一线治疗肝癌病人的客观缓解率、完全缓解率、部分缓解率、疾病稳定率、疾病进展率、治疗起效时间分别为41.9%(18/43)、16.3%(7/43)、25.6%(11/43)、37.2%(16/43)、20.9%(9/43)、2.2个月(2.0个月,3.5个月),中位缓解持续时间尚未达到。16例进行二线治疗肝癌病人的客观缓解率、完全缓解率、部分缓解率、疾病稳定率、疾病进展率、治疗起效时间、中位缓解持续时间分别为4/16、0、4/16、6/16、6/16、3.8个月(3.6个月,4.1个月)、4.2个月(95%CI为2.0~6.3个月)。59例肝癌病人中,6例肿Objective To investigate the clinical efficacy of the combination therapy of lenvatinib and programmed death-1(PD-1)antibodies in unresectable or advanced hepatocellular carcinoma(HCC).Methods The retrospective and descriptive study was conducted.The clinico-pathological data of 59 patients with unresectable or advanced HCC who were admitted to Zhongshan Hospital of Fudan University from September 2018 to January 2020 were collected.There were 54 males and 5 females,aged from 25 to 73 years,with a median age of 52 years.All 59 patients underwent combination therapy with lenvatinib and PD-1 antibodies including 43 cases undergoing first-line therapy and 16 cases who cannot tolerate first-line therapy or with tumor progressed after first-line therapy undergoing second-line therapy.Observation indicators:(1)clinical efficacy;(2)adverse drug reactions and treatment;(3)follow-up and survival.Follow-up was performed using outpatient examination or telephone interview to detect tumor diameter of the target lesion,overall survival and progression free survival of patients up to December 2020.Measurement data with skewed distribution were expressed as M(P25,P75)or M(range).Count data were represented as absolute numbers and(or)percentages.The Kaplan-Meier method was used to calculate the median duration of response(DoR),median overall survival time,median progression free survival time,survival rates and draw survival curves.Results(1)Clinical efficacy:the objective response rate(ORR),complete response rate(CR),partial response rate(PR),stable disease rate(SD),progression disease rate(PD),time to response(TTR)and median DoR of 59 HCC patients were 37.3%(22/59),11.9%(7/59),25.4%(15/59),37.3%(22/59),25.4%(15/59),2.6 months(2.1 months,4.0 months),6.3 months[95%confidence interval(CI)as 2.2 to 10.5 months],respectively.The ORR,CR,PR,SD,PD and TTR of 43 HCC patients undergoing first-line therapy were 41.9%(18/43),16.3%(7/43),25.6%(11/43),37.2%(16/43),20.9%(9/43),2.2 months(2.0 months,3.5 months),respectively.The median DoR of

关 键 词：肝肿瘤 不可切除肝细胞癌 联合治疗 仑伐替尼 程序性死亡受体⁃1抗体 

分 类 号：R735.7[医药卫生—肿瘤]