多纳非尼片联合抗PD-1单抗和经导管动脉化疗栓塞术治疗不可手术切除的肝细胞癌的临床研究  

Clinical trial of donafenib combined with anti-PD-1 monoclonal antibody and transarterial chemoembolization in patients with unresectable hepatocellular carcinoma

作　　者：古善智[1] 黄满平[1] 谭玉林[2] 胡鸿涛[3] 朱旭[4] 郑桐森[5] 郑振东 袁牧 GU Shanzhi;HUANG Manping;TAN Yulin;HU Hongtao;ZHU Xu;ZHENG Tongsen;ZHENG Zhendong;YUAN Mu(Department of Interventional Radiology,Hunan Cancer Hospital,Changsha 410013,China)

机构地区：[1]湖南省肿瘤医院介入科,长沙410013 [2]蚌埠医学院第一附属医院介入科,233004 [3]河南省肿瘤医院微创介入科,450003 [4]北京大学肿瘤医院介入治疗科,100142 [5]哈尔滨医科大学附属肿瘤医院消化内科,150081 [6]解放军北部战区总医院肿瘤科,110016

出　　处：《临床肿瘤学杂志》2023年第7期609-614,共6页Chinese Clinical Oncology

摘　　要：目的探讨多纳非尼联合抗程序性死亡受体1(PD-1)单抗和经导管动脉化疗栓塞术(TACE)在不能手术切除的肝细胞癌(HCC)患者中的安全性、耐受性和初步有效性。方法这项前瞻性、多中心、开放的临床研究(注册号:NCT04605185)纳入2021年1月至2022年5月既往未接受过系统治疗的不可手术切除的HCC患者,接受多纳非尼联合特瑞普利单抗和TACE。主要研究终点为多纳非尼的最佳Ⅱ期推荐剂量(RP2D),次要终点包括安全性和耐受性,基于改良RECIST(mRECIST)标准评价近期疗效、无进展生存时间(PFS)和总生存时间(OS)。本研究分为剂量递增组和剂量扩展组,剂量递增组得到RP2D后,后续纳入的患者进入剂量扩展组。结果共纳入31例受试者,剂量递增阶段12例,剂量扩展阶段19例。多纳非尼的RP2D为100mg每天2次,未观察到剂量限制性毒性。31例受试者均发生与治疗相关的不良事件(TRAE),14例受试者发生3级TRAE,无4级或5级TRAE发生。主要TRAE包括肝功能异常、腹痛和血小板减少。发生率最高的3级TRAE为肝功能异常和血压升高。随访截止于2022年10月,全部受试者中位随访194天,中位TACE治疗2次。共27例合格受试者,获CR 5例、PR 15例、SD 4例、PD 3例;客观缓解率为74.1%,疾病控制率为88.9%。全组1年无进展生存率为62.2%,1年生存率为96.3%,中位PFS和中位OS未达到。结论TACE联合多纳非尼和特瑞普利单抗对于不可手术切除的HCC患者具有较好的安全性和较高的客观缓解率。Objective To explore the safety,tolerability and preliminary efficacy of donafenib combined with anti-programmed death receptor 1(PD-1)monoclonal antibody and transcatheter arterial chemoembolization(TACE)in patients with unresectable hepatocellular carcinoma(HCC).Methods This prospective,multicenter,open-label clinical study(registration number:NCT04605185)enrolled patients with unresectable HCC who had not previously received systemic therapy from January 2021 to May 2022.The patients were given donafenib in combination with toripalimab and TACE.The primary endpoint was the optimal phase II recommended dose(RP2D)of donafenib,with secondary endpoints including safety and tolerability,short-term efficacy based on modified RECIST(mRECIST)criteria,progression-free survival(PFS)and overall survival(OS).Patients were divided into a dose escalation group and a dose expansion group.After RP2D was obtained in the dose escalation group,the subsequent patients were admitted to the dose expansion group.Results A total of 31 subjects were enrolled,including 12 in the dose escalation group and 19 in the dose expansion group.The RP2D of donafenib was 100 mg twice a day,and dose-limiting toxicity was not observed.Treatment-related adverse events(TRAEs)occurred in all 31 subjects,and grade 3 TRAE occurred in 14 subjects,and no grade 4 or 5 TRAE occurred.The main TRAEs included abnormal liver function,abdominal pain and thrombocytopenia.Grade 3 TRAE with the highest incidence was abnormal liver function and elevated blood pressure.Follow-up ended in October 2022,with a median follow-up of 194 days for all subjects and the median TACE treatment of twice.A total of 27 subjects were eligible for efficacy evaluation,and among them,there were 5 cases of CR,15 cases of PR,4 cases of SD and 3 cases of PD;The objective response rate was 74.1%and the disease control rate was 88.9%.The 1-year progression-free survival rate was 62.2%and the 1-year survival rate was 96.3%,and the median PFS and median OS were not reached.Conclusion TACE com

关 键 词：肝细胞癌 多纳非尼 经导管动脉化疗栓塞术 安全性 疗效 

分 类 号：R735.7[医药卫生—肿瘤]