经动脉化疗栓塞联合卡瑞利珠单抗及酪氨酸激酶抑制剂治疗中晚期肝细胞癌的安全性及近期疗效

Transarterial chemoembolization combined with camrelizumab and tyrosine kinase inhibitor for advanced hepatocellular carcinoma:its safety and short-term efficacy

目的评价动脉化疗栓塞术(TACE)联合卡瑞利珠单抗(Camrelizumab)及酪氨酸激酶抑制剂(TKI)治疗中晚期肝细胞癌(HCC)患者的安全性及有效性。方法回顾性分析2019年8月至2021年2月接受TACE、Camrelizumab、TKI联合治疗的33例HCC患者的临床资料。根据美国国家癌症研究所常见不良事件评价标准(CTCAE)5.0版记录出现不可接受的毒性或疾病进展前各类不良事件发生情况;根据实体瘤改良反应评估标准(mRECIST)评估肿瘤反应,包括完全缓解(CR)、部分缓解(PR)、疾病稳定(SD)和疾病进展(PD),并计算肿瘤客观缓解率(ORR)、疾病控制率(DCR);统计分析无进展生存期(PFS)及至疾病进展时间(TTP)。结果33例患者的中位随访时间为15.1个月(95%CI:9.5~18.0),共29例(87.9%)患者发生了不良事件。主要为肝功能损伤17例(51.5%)、反应性皮肤毛细血管增生症(RCCEP)14例(42.5%)、皮疹13例(39.3%)、甲状腺功能减退12例(36.3%)。有5例(15.2%)患者出现了3级不良事件,主要为肝功能损伤(9.1%)。不良事件导致2例患者TKI减量,1例患者暂停免疫治疗1次,3例患者因无法缓解的严重不良事件而永久停药。33例患者中,4例(12.1%)获得CR,20例(60.6%)获得PR,3例(9.1%)获得SD,ORR为72.7%,DCR为81.8%。中位PFS为9.2个月(95%CI:5.9~12.5)、中位TTP为7.7个月(95%CI:3.3~12.1)。结论TACE联合Camrelizumab及TKI治疗中晚期HCC严重不良事件发生率较低、肿瘤控制率较高、至疾病进展时间延长,有望为中晚期肝癌生存延长提供治疗选择。

Objective To evaluate the safety and efficacy of transarterial chemoembolization(TACE)combined with camrelizumab and tyrosine kinase inhibitor(TKI)in treating advanced hepatocellular carcinoma(HCC).Methods The clinical data of 33 patients with advanced HCC,who received TACE combined with camrelizumab and TKI in a single center between August 2019 and February 2021,were retrospectively analyzed.According to National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE)version 5.0,all types of adverse events before the occurrence of unacceptable toxicity or disease progression were recorded.Based on the modified Response Evaluation Criteria for Solid Tumors(mRECIST),the tumor response,including complete response(CR),partial response(PR),stable disease(SD)and progressive disease(PD),was evaluated.The objective response rate(ORR)and disease control rate(DCR)of HCC were calculated.The progression-free survival(PFS)and time to disease progression(TTP)were statistically analyzed.Results The median follow-up time was 15.1 months(95%CI:9.5~18.0 months).Adverse events occurred in 29 patients(87.9%),mainly including liver function injury(n=17,51.5%),reactive cutaneous capillary endothelial proliferation(RCCEP,n=14,42.5%),skin rash(n=13,39.3%),and hypothyroidism(n=12,36.3%).Five patients(15.2%)developed adverse events of grade Ⅲ,which were mainly the liver function impairment(9.1%).Due to the occurrence of adverse events,the TKI dose had to be reduced in 2 patients and immunotherapy treatment had to be stopped one time in one patient;besides,medication had to be stopped permanently in 3 patients due to serious adverse events that could not be alleviated.Among the 33 patients,CR was obtained in 4(12.1%),PR in 20(60.6%),SD in 3(9.1%).The ORR and DCR were 72.7%and 81.8%respectively.The median PFS and median TTP was 9.2 months(95%CI:5.9-12.5 months)and 7.7 months(95%CI:3.3-12.1 months)respectively.Conclusion For the treatment of advanced HCC,TACE combined with camrelizumab and TKI carries lower incidence of serious adverse events,higher tumor control rate and longer TTP.It is expected that this therapeutic method can provide advanced HCC patients with treatment option to prolong their survival.