PD-1/PD-L1抗体与多西他赛治疗晚期非小细胞肺癌安全性Meta分析  

Safety of PD-1/PD-L1 antibody versus docetaxel for advanced non-small cell lung cancer:A Meta analysis

作　　者：苏强[1] 闫涵[1] 侯艳丽[1] 肖婧[1] 甄洪超[1] 张晨光[2] 曹邦伟[1] 

机构地区：[1]首都医科大学附属北京友谊医院肿瘤科,北京100050 [2]首都医科大学基础学院生化教研室,北京100069

出　　处：《中华肿瘤防治杂志》2016年第21期1450-1454,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然基金面上项目(81272615);首都医科大学临床与基础合作课题(15JL33);首都医科大学附属北京友谊医院院启动基金(yyqdkt2014-12)

摘　　要：目的非小细胞肺癌（non-small cell lung cancer,NSCLC）是肺癌最常见的病理类型,目前免疫疗法是其研究热点。本研究对程序细胞死亡蛋白-1（programmed cell death protein 1,PD-1）及其配体（programmed cell death ligand 1,PD-L1）抗体与多西他赛在晚期NSCLC二线以上治疗中的安全性进行比较。方法计算机检索PubMed、EMbase、CBM、CNKI、VIP和WanFang Data数据库截止到2016-05,公开发表的PD-1/PD-L1抗体与多西他赛在晚期非小细胞肺癌治疗中的Ⅱ/Ⅲ期病例对照临床试验文献,通过文献筛选,提取数据,采用RevMan 5.3软件对纳入文献进行Meta分析。应用STATA 12.0对发表偏倚进行分析。结果 PD-1/PD-L1抗体组与多西他赛组相比,1-4级的总不良反应、粒细胞减少、贫血、恶心、疲乏反应较低,其中总不良反应的合并相对危险度（risk ratio,RR）和95%置信区间（confidence interval,95%CI）为0.78（0.74-0.81）,粒细胞减少为0.02（0.01-0.05）,贫血为0.21（0.12-0.35）,恶心为0.54（0.44-0.65）,疲乏为0.56（0.47-0.65）。但免疫相关不良反应如皮疹、肺炎、甲状腺功能亢进和甲状腺功能减退的风险较高,皮疹RR（95%CI）为2.01（1.14-3.51）,肺炎为3.19（1.9-5.34）,甲状腺功能亢进为5.1（2.23-11.68）,甲状腺功能减退为23.36（8.04-67.90）。结论在晚期非小细胞肺二线以上治疗中,PD-1/PD-L抗体组的不良反应包括粒细胞减少等发生风险明显低于多西他赛组;而免疫相关不良反应发生风险高。OBJECTIVE Non-small cell lung cancer（NSCLC）is the most common pathological type of lung cancer,and now immune therapy is the current focus.This systematic review was conducted to compare the safety of PD-1/PD-L1 antibody with chemotherapy docetaxel alone in advanced NSCLC.METHODS Scientific databases were searched for relevant controlled clinical trials comparing the safety of PD-1/PD-L1 antibody with docetaxel.PhaseⅡ/Ⅲrandomized controlled trials were selected in which patients suffering advanced NSCLC were randomized to receive PD-1/PD-L1 antibody versus docetaxel alone.Meta analyses were performed using Review Manager 5.3and STATA 12.RESULTS After exclusion of non-eligible citations,a total of 4clinical randomized controlled trials were eligible for the meta analysis.The risk ratio（RR）and 95% Confidence interval（95%CI）of PD-1/PD-L1 antibody over docetaxel were 0.78（0.74-0.81）for all-grade adverse events,0.02（0.01-0.05）for all-grade neutropenia,0.21（0.12-0.35）for all-grade anemia,0.54（0.44-0.65）for all-grade nausea,and 0.56（0.47-0.65）for all-grade fatigue,respectively.However,the RR and95%CI of PD-1/PD-L1 antibody were 2.01（1.14-3.51）for rash,3.19（1.9-5.34）for pneumonitis,5.1（2.23-11.68）for hyperthyroidism,and 23.36（8.04-67.90）for hypothyroidism compared with that of docetaxel.CONCLUSIONS The incidence of adverse events of grad 1-4and 3-4like neutropenia were significantly lower in advanced NSCLC patients receiving PD-1/PD-L1 antibody than those taking docetaxel while the incidence of immune related adverse events were obviously higher thanthat of docetaxel.

关 键 词：PD-1抗体 PD-L1抗体 多西他赛 非小细胞肺癌 NSCLC META分析 

分 类 号：R734.2[医药卫生—肿瘤]