仑伐替尼、PD-1抑制剂联合肝动脉栓塞灌注化疗治疗不可切除肝癌疗效  

Efficacy of lenvatinib,PD-1 inhibitor combined with transcatheter arterial chemoembolization in treatment of unresectable hepatocellular carcinoma

作　　者：杨宇光 唐辉 谭志明 麦聪 陈铁军 唐云强 Yang Yuguang;Tang Hui;Tan Zhiming;Mai Cong;Chen Tiejun;Tang Yunqiang(Department of Hepatobiliary Surgery,Affiliated Cancer Hospital and Institute of Guangzhou Medical University,Guangzhou 510095,China;Department of Quality Control,Affiliated Cancer Hospital and Institute of Guangzhou Medical University,Guangzhou 510095,China)

机构地区：[1]广州医科大学附属肿瘤医院肝胆外科,510095 [2]广州医科大学附属肿瘤医院质控科,510095

出　　处：《中华肝脏外科手术学电子杂志》2023年第1期55-60,共6页Chinese Journal of Hepatic Surgery(Electronic Edition)

基　　金：广州市卫生局一般引导项目(20171A011317);湖北陈孝平发展科技发展基金会(CXPJJH1200008-12)。

摘　　要：目的探讨仑伐替尼、PD-1抑制剂联合肝动脉栓塞灌注化疗(TACE-HAIC)治疗不可切除肝细胞癌(肝癌)的临床疗效。方法回顾性分析2019年9月1日至2021年2月1日在广州医科大学附属肿瘤医院诊治的69例肝癌患者临床资料。其中男64例,女5例;平均年龄(51±12)岁。37例患者接受仑伐替尼、PD-1抑制剂联合TACE-HAIC治疗(TAHPLa组),32例患者接受索拉非尼联合TACE治疗(SoraTACE组)。患者均签署知情同意书,符合医学伦理学规定。观察两组手术转化率、肿瘤反应情况、治疗相关不良反应情况、生存情况等。生存分析采用Kaplan-Meier法和Log-rank检验。生存影响因素分析采用Cox回归模型。结果TAHPLa组手术转化率为30%(11/37),明显高于SoraTACE组的3%(1/32)(χ^(2)=8.454,P<0.05)。根据实体肿瘤临床疗效评价标准修订版(mRECIST),TAHPLa组客观缓解率为70%(26/37),明显高于SoraTACE组的31%(10/32)(χ^(2)=10.470,P<0.05)。总体不良反应事件中,TAHPLa组疲劳、恶心、感觉神经性病变、血小板减少症发生率分别为46%(17/37)、54%(20/37)、27%(10/37)、41%(15/37),明显高于SoraTACE组的19%(6/32)、16%(5/32)、0、9%(3/32)(χ^(2)=5.711,10.968,8.051,8.644;P<0.05);TAHPLa组手足综合征发生率为8%(3/37),明显低于SoraTACE组的28%(9/32)(χ^(2)=4.786,P<0.05)。3~4级不良反应事件中,TAHPLa组血小板减少症发生率为24%(9/37),明显高于SoraTACE组的3%(1/32)(χ^(2)=4.630,P<0.05)。两组均未出现治疗相关死亡。TAHPLa组中位无进展生存期(PFS)、总体生存期(OS)分别为10.3、27.8个月,SoraTACE组相应为5.1、10.7个月,差异有统计学意义(χ^(2)=10.871,27.539;P<0.05)。Cox多因素分析显示,TAHPLa治疗是患者PFS和OS的独立影响因素(HR=0.053,0.179;P<0.05)。结论对于不可切除肝癌,与索拉非尼联合TACE治疗相比,仑伐替尼、PD-1抑制剂联合TACE-HAIC治疗安全性良好,可提高手术转化率,延长患者生存时间。Objective To evaluate the clinical efficacy of the combination of lenvatinib,PD-1 inhibitor and transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy(TACE-HAIC)in the treatment of unresectable hepatocellular carcinoma(HCC).Methods Clinical data of69 HCC patients admitted to the Affiliated Cancer Hospital of Guangzhou Medical University from September 1,2019 to February 1,2021 were retrospectively analyzed.Among them,64 patients were male and 5 female,aged(51±12)years on average.37 patients were treated with lenvatinib,PD-1 inhibitor combined with TACE-HAIC(TAHPLa group),and 32 patients received sorafenib combined with TACE(SoraTACE group).The informed consents of all patients were obtained and the local ethical committee approval was received.The surgical conversion rate,tumor response,treatment-associated adverse reactions,and survival were observed between two groups.Survival analysis was performed by Kaplan-Meier method and Log-rank test.The influencing factors of survival were identified by Cox's regression model.Results In the TAHPLa group,surgical conversion rate was 30%(11/37),significantly higher than 3%(1/32)in the SoraTACE group(χ^(2)=8.454,P<0.05).According to the modified response evaluation criteria in solid tumors(mRECIST),the objective remission rate in the TAHPLa group was 70%(26/37),significantly higher than 31%(10/32)in the SoraTACE group(χ^(2)=10.470,P<0.05).Regarding the overall adverse events,the incidence of fatigue,nausea,sensory neuropathy and thrombocytopenia in the TAHPLa group was 46%(17/37),54%(20/37),27%(10/37)and 41%(15/37),significantly higher than 19%(6/32),16%(5/32),0 and 9%(3/32)in the SoraTACE group(χ^(2)=5.711,10.968,8.051,8.644;P<0.05);The hand-foot syndrome in the TAHPLa group was 8%(3/37),significantly lower than 28%(9/32)in the SoraTACE group(χ^(2)=4.786,P<0.05).In terms of grade 3-4 adverse reactions,the incidence of thrombocytopenia in the TAHPLa group was 24%(9/37),significantly higher than 3%(1/32)in the SoraTACE group(χ^(2)=4.630,P<0

关 键 词：癌 肝细胞 肝动脉灌注化疗 肝动脉栓塞化疗 仑伐替尼 程序性死亡受体-1 

分 类 号：R73[医药卫生—肿瘤]