从临床试验角度探讨TACE联合索拉非尼在肝癌治疗中的应用价值

Application value of TACE combined with sorafenib for primary liver cancer from the perspective of clinical trials

目的从临床试验角度探讨TACE联合索拉非尼在肝癌治疗中的应用价值。方法选择2010年~2018年全球范围内TACE联合索拉非尼治疗肝癌的4个证据级别最高的随机对照试验(Post-TACE、SPACE、TACE-2、TACTICS研究)。采用对比陈述的方法,分析入组患者人数、肿瘤情况、肝功能、全身状况等一般资料及TACE治疗方式、用药持续时间、主要观察终点、评价方法、中位随访时间等资料,进一步对比不同联合模式下患者的临床获益,找出TACE联合索拉非尼的最佳模式和优选人群。文献综述中采用Kaplan-Meier法绘制生存曲线,采用Cox比例风险回归模型分析比较两组生存状况。结果Post-TACE、SPACE、TACE-2研究均以阴性结果告终。TACTICS研究发现,TACE联合索拉非尼组的中位血管侵犯时间、中位肝外转移时间和TACE时间间隔分别为31.3、15.7个月和21.1周,明显长于单纯TACE组的4.0、6.9个月和16.9周(HR=0.26,0.21,0.59;P=0.008,0.006,0.018)。结论从临床试验视角来看,TACE联合索拉非尼可能延长不可切除的早中期肝癌患者的无进展生存期,对肿瘤进展起到稳定作用。

Objective To investigate the application value of TACE combined with sorafenib in the treatment of primary liver cancer(PLC)from the perspective of clinical trials.Methods Four randomized controlled trials of TACE combined with sorafenib for PLC with the highest evidence level from 2010 to 2018 were selected globally,named Post-TACE,SPACE,TACE-2,TACTICS study respectively.Using the method of comparative description,the number of patients,tumor condition,liver function,general condition,TACE operation,duration of medication,primary endpoint,evaluation method and median followup time were analyzed.The clinical benefits of patients were further compared between different combinations of TACE with sorafenib to explore the optimal one and most eligible patients.In the literature review,the survival curve was delineated by Kaplan-Meier method.The survival status between two groups was analyzed by Cox's proportional hazards regression model.Results Negative results were obtained in Post-TACE,SPACE and TACE-2 studies.TACTICS study showed that the median vascular invasion time,median extrahepatic metastasis time and TACE time interval in the TACE combined with sorafenib group were 31.3 months,15.7 months and 21.1 weeks,respectively,significantly longer than 4.0 months,6.9 months and 16.9 weeks in the single TACE group(HR=0.26,0.21,0.59;P=0.008,0.006,0.018).Conclusions From the perspective of clinical trials,TACE combined with sorafenib may prolong the progression-free survival of patients with unresectable early and middle stage PLC and play a role in stabilizing the tumor progression.