仑伐替尼联合TACE和PD-1单抗治疗复发肝癌的安全性与有效性探索

Exploration of safety and efficacy of lenvatinib in combination with TACE and PD-1antibody in treatment of recurrent liver cancer

目的 对仑伐替尼联合经肝动脉化疗栓塞(transarterial chemoembolization,TACE)和程序性死亡受体1(programmed death-1,PD-1)单抗治疗复发肝癌的安全性与有效性进行初步探索。方法 回顾性分析2019年1月至2022年1月期间四川大学华西医院肝脏外科/肝移植中心收治的不可切除复发肝癌并接受仑伐替尼+TACE+PD-1单抗转化治疗的22例患者的临床资料。结果 22例患者均出现一定程度的不良反应事件,3级不良反应事件率为18.2%(4/22),未出现4级及以上不良反应事件。依据修改后实体瘤疗效评定标准(modified response evaluation criteria solid tumors,mRECIST),在治疗后第4个月时评估,完全缓解(complete response,CR)2例,部分缓解(partial response,PR)5例,疾病稳定(stable disease,SD)6例,疾病进展(progressive disease,PD)9例,客观缓解(CR+PR)率(objective response rate,ORR)为31.8%(7/22);末次随访时评估,CR 1例,PR 5例,SD 1例,PD 15例,ORR为27.3%(6/22)。22例患者的1年总体生存(overall survival,OS)率为83.8%,1年无进展生存(progression-free survival,PFS)率为38.2%。亚组分析中,肝内病灶组(16例)患者的1年OS率为86.2%[95%CI(77.1%,95.3%)]、1年PFS率为46.9%[95%CI(34.0%,59.8%)],肝内外病灶组(6例)患者的1年OS率为75.0%[95%CI(53.3%,96.7%)]、1年PFS率为16.7%[95%CI(15.0%,31.9%)],肝内病灶组和肝内外病灶组的OS(P=0.864)和PFS(P=0.125)情况比较差异均无统计学意义;依据mRECIST标准评估,肝内外病灶组的ORR相较于肝内病灶组更低[0%(0/6)比43.8%(7/16),P=0.049]。结论 仑伐替尼联合TACE及PD-1单抗治疗不可切除复发肝癌是安全有效的,但仍存在许多问题值得进一步探索。

Objective To explore the safety and efficacy of lenvatinib in combination with transarterial chemoembolization(TACE) and programmed death receptor 1(PD-1) antibody in the treatment of recurrent liver cancer.Method The clinical data of 22 patients with unresectable recurrent liver cancer admitted to Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University and received the conversion therapy of lenvatinib+TACE+PD-1 antibody between January 2019 and January 2022 were retrospectively analyzed. Results All22 patients experienced some degree of adverse events, with a grade 3 adverse event rate of 18.2%(4/22) and no grade 4 or higher adverse events. At 4 months of treatment, according to the modified response evaluation criteria solid tumors(mRECIST), 2 cases were in complete response(CR), 5 cases were in partial response(PR), and 6 cases were in stable disease(SD), 9 cases were in progressive disease(PD), and the objective response(CR+PR) rate(ORR) was 31.8%(7/22).At the last follow-up, there was 1 case in CR, 5 cases in PR, 1 case in SD, and 15 cases in PD, with an ORR of 27.3%(6/22).The 1-year overall survival(OS) rate was 83.8% and the 1-year progression-free survival(PFS) rate was 38.2%. In the subgroup analysis, the 1-year OS rate for patients with recurrent liver cancer with intrahepatic lesions(n=16) only was86.2% [95%CI(77.1%, 95.3%)], the 1-year PFS rate was 46.9% [95%CI(34.0%, 59.8%)], and the ORR based on mRECIST criteria was 43.8%(7/16). Patients with intrahepatic combined with extrahepatic lesions(n=6) had a 1-year OS rate of75.0% [95%CI(53.3%, 96.7%)] and a 1-year PFS rate of 16.7% [95%CI(15.0%, 31.9%)], and the ORR based on mRECIST criteria was 0%(0/6). There were no significant differences in OS(P=0.864) and PFS(P=0.125) between the two subgroups. The ORR of intrahepatic combined with extrahepatic lesions group was worse compared to the intrahepatic lesion group(P=0.049). Conclusion Lenvatinib in combination with TACE and PD-1 antibody is safe and effective in the treatment of unresectable recurrent liver cancer, but there are still many issues that deserve further exploration.