联合治疗方案在术后难治性复发肝癌中的临床治疗价值

Efficency and safety of various combined therapies in treating postoperative refractory recurrent liver cancer

目的比较联合应用程序性死亡蛋白-1(PD-1)抗体和酪氨酸激酶抑制剂(TKI)的二联疗法与联合应用PD-1抗体、TKI和局部治疗的三联疗法对术后难治性复发肝癌的有效性和安全性。方法回顾性收集并分析2016年7月至2019年3月在解放军总医院第一医学中心接受二联疗法与三联疗法治疗的肝癌肝切除术后难治性复发患者资料。使用改良后实体瘤疗效评价标准评估两组患者疗效,比较生存率、疾病控制率(DCR)等指标,并根据美国国立癌症研究所《不良事件常用术语标准》记录不良反应事件。结果共纳入63例患者,其中二联疗法组25例,男性16例,女性9例,年龄(54.3±8.8)岁;三联疗法组38例,男性31例,女性7例,年龄(55.5±8.4)岁。三联疗法组患者的1年总生存率(94.5%)高于二联疗法组(54.9%),差异具有统计学意义(P<0.01)。二联疗法组和三联疗法组的DCR分别为64.0%(16/25)和84.2%(32/38),差异无统计学意义(P>0.05)。二联疗法组和三联疗法组的肿瘤治疗相关不良事件发生率分别为80.0%(20/25)和78.9%(30/38),且二组均未发生治疗相关死亡。结论PD-1抗体和TKI二联疗法及PD-1抗体、TKI和局部治疗三联疗法治疗术后难治性复发肝癌是安全有效的,后者在生存率方面有更好的临床获益。

Objective The study aimed to study the efficacy and safety of combined dual therapy using anti-programmed death(PD)-1 and tyrosine kinase inhibitor(TKI)with combined triple therapy using anti-PD-1,TKI and locoregional intervention triple therapy in patients with postoperative refractory recurrent liver cancer.Methods Patients with postoperative refractory recurrent liver cancer who had undergone either anti-PD-1 and TKI dual therapy or anti-PD-1,TKI and locoregional intervention triple therapy between July 2016 and March 2019 at the First Medical Center,Chinese PLA General Hospital were retrospectively studied.Tumor responses were assessed by the modified response evaluation criteria in solid tumors and overall survival and progression free survival were compared.Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events.Results Of 63 patients who were included in this study,there were 25 patients in the dual therapy group(16 males and 9 females,aged 54.3±8.8 years)and 38 patients in the triple therapy group(31 males and 7 females,aged 55.5±8.4 years).The 1-year survival rate of the triple therapy group was significantly higher than the dual therapy group(94.5%vs 54.9%)(P<0.01).The disease control rate was 64.0%(16/25)in the dual therapy group and 84.2%(32/38)in the triple therapy group,and the difference was not significant(P>0.05).The incidence of treatment-related adverse events in the triple therapy group and the dual therapy group were 78.9%(30/38)and 80%(20/25),respectively.There was no treatment-related death in the 2 groups.Conclusions Anti-PD-1 and TKI dual therapy and anti-PD-1,TKI and locoregional intervention triple therapy were effective and tolerable treatments for postoperative refractory recurrent liver cancer.The latter treatment had a significantly better clinical benefit on survival outcomes.