【摘要】 目的贝伐珠单抗(bevacizumab,B)及厄洛替尼(erlotinib,E)作用于不同的靶点,在抗肿瘤机制中有相互补充的作用,本研究通过Meta分析比较贝伐珠单抗联合厄洛替尼(B+E)与贝伐珠单抗单药治疗(Bevacizumab,B)或联合化疗(B+chem)对非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的疗效及安全性。方法计算机检索Medline、web of science、Cochrane library和EMbase等数据库,结合手工检索,检索时间至2016-12-18,收集比较B+E与B或B+chem治疗NSCLC的临床试验,按照Cochrane系统评价方法,采用RevMan 5.3软件进行Meta分析,分析了无进展生存期(progression-free-survival,PFS)、总生存期(overall survival,OS)和不良事件(adverse event)等结局指标。结果共纳入6项临床试验。B+E与B单药治疗相比,能够提高患者的PFS,HR=0.65,95%CI为0.57~0.74;两组OS差异无统计学意义,HR=0.96,95%CI为0.83~1.11。对于EGFR突变的患者,B+E与B单药治疗相比,能够提高患者的PFS,HR=0.43,95%CI为0.30~0.61;而在EGFR野生型患者中,B+E与B单药治疗PFS差异无统计学意义,HR=0.85,95%CI为0.70~1.04。而B+E与B+chem治疗相比,B+E组PFS(HR=1.88,95%CI为1.45~2.44)及OS(HR=1.36,95%CI为1.03~1.79)均显著低于B+chem组。EGFR突变的患者,B+E与B+chem相比,PFS差异无统计学意义,HR=0.58,95%CI为0.22~1.55)。而在EGFR野生型患者中,B+E与B+chem相比,PFS更短,HR=1.96,95%CI为1.37~2.82。B+E方案可能会增加患者发生3~4级皮疹及腹泻的可能。结论在NSCLC患者中,B+E治疗方案与B单药治疗相比具有更好的疗效,然而与B+chem方案相比,B+E方案仅在EGFR突变患者中具有更好的疗效。结果仍需大样本量研究证实。更多还原

【Abstract】 OBJECTIVE Bevacizumab and erlotinib target in different pathways,and both exhibit beneficial effects in the treatment of non-small cell lung cancer(NSCLC).We conducted a meta-analysis to evaluate the efficacy and safety of bevacizumab combined Erlotinib(B+E)versus bevacizumab alone(B)or bevacizumab combined chemotherapy(B+chem)in NSCLC.METHODS Databases including Medline,Cochrane library,web of science,EMbase were searched,and the relevant periodicals were also manually searched to collect the relevant randomized controlled trials.The main outcome measures included overall survival(OS),progression-free survival(PFS)and adverse events.Meta-analysis was performed using RevMan 5.3software according to the Cochrane Handbook.RESULTS Six RCTs were included in this meta-analysis.The combination of bevacizumab and erlotinib significantly improved PFS[HR=0.65(0.57-0.74)compared with bevacizumab alone but had no significant difference in OS [HR=0.96(0.83-1.11)].B+E improved PFS compared with B in EGFR mutation patients[HR=0.43(0.30-0.61)]and no significant difference in EGFR wild type patients[HR:0.85(0.70-1.04)].Compared with B+chem,B+E had lower PFS [HR=1.88(1.45-2.44)and OS[HR=1.36(1.03-1.79)].PFS in B+E had no significant difference compared with B+chem in EGFR mutation patients[HR=0.58(0.22-1.55)]and was lower in EGFR wild type patients[HR=1.96(1.37-2.82)].The incidence of grade 3/4adverse events such as rash and diarrhoea was higher in B+E group than in the B/B+chem group.CONCLUSIONS The combination of bevacizumab and erlotinib can significantly improve PFS and OS compared with bevacizumab alone but might have no superiority compared with combination of bevacizumab with chemotherapy.Further well conducted,large-scale trials are needed to validate these findings.更多还原