EGFR-TKIs联合贝伐珠单抗治疗非小细胞肺癌疗效及安全性的Meta分析

目的:系统评价第一代EGFR-TKIs联合贝伐珠单抗治疗不可切除局部晚期及转移性EGFR敏感突变非小细胞肺癌的疗效及安全性。方法:计算机检索Pubmed、Cochrane Library、EMbase、CBM、CKNI、万方数据库等数据库，检索时间为建库至2019年09月，按照严格的纳入和排除标准筛选文献和提取资料后，采用RevMan 5.3软件进行Meta分析。结果:最终纳入9篇文献，包括1 482名患者。这项研究终点是中位无进展生存期、客观缓解率、疾病控制率及安全性。Meta分析结果显示，第一代EGFR-TKIs联合贝伐珠单抗较EGFR-TKIs单药能有效改善不可切除局部晚期及转移性EGFR敏感突变非小细胞肺癌疾病控制率(disease control rate，DCR)［比值比（odds ratio，OR）=1.86，95%可信区间（confidence interval，CI）(1.40，2.46),P<0.000 1］、客观缓解率（objective response rate，ORR）［OR=1.90，95%CI(1.46，2.48),P<0.000 01］、中位无进展生存期（median progression free survival，mPFS）［风险比（hazard ratio，HR）=0.62，95%CI(0.54，0.71),P<0.000 01］，差异有统计学意义。安全性方面:Ⅲ级及以上不良反应，联合治疗组皮疹［OR=1.64，95%CI(1.20，2.24),P=0.002］、高血压［OR=6.50，95%CI(4.07，10.39),P<0.000 01］、蛋白尿［OR=9.87，95%CI(2.97，32.81),P=0.000 2］发生率高于EGFR-TKIs单药组，差异有统计学意义；腹泻［OR=1.09，95%CI(0.54，2.17),P=0.82］、出血事件［OR=1.74，95%CI(0.74，4.09),P=0.21］发生率差异无统计学意义。结论:在治疗不可切除局部晚期及转移性EGFR敏感突变非小细胞肺癌时，第一代EGFR-TKIs联合贝伐珠单抗与EGFR-TKIs单药相比能有效改善疾病控制率、客观缓解率及中位无进展生存期,不良反应主要有皮疹、高血压、蛋白尿，试验组发生率高于对照组，差异有统计学意义。

Meta-analysis of the efficacy and safety of EGFR-TKIs plus Bevacizumab versus EGFR-TKIs alone in non-small cell lung cancer

Objective:To evaluate the efficacy and safety of EGFR-TKIs plus Bevacizumab verse EGFR-TKIs alone in advanced non-small cell lung cancer.Methods:The PubMed,Cochrane Library,Embase,CBM,CNKI,WanFang Data were electronically searched to collect randomized controlled trails.The search time ranged from inception to September 2019.After screening the literature and extracting data strictly，Meta-analysis was performed by RevMan 5.3.The endpoint of this study was median progression-free survival (mPFS),objective response rate (ORR),disease control rate (DCR) and security.Results:A total of 9 articles were included,including 1 482 patients.Meta-analysis showed that the treatment of EGFR-TKIs plus Bevacizumab could improve the disease control rate (DCR) ［OR=1.86,95%CI(1.40，2.46),P<0.000 1］ and objective response rate (ORR) ［OR=1.90,95%CI(1.46，2.48),P<0.000 01］ in advanced non-small cell lung cancer compared with the treatment of EGFR-TKIs alone,the difference was statistically significant.Meanwhile,median progression-free survival (mPFS) ［HR=0.62,95%CI(0.54，0.71),P<0.000 01］ was different,and the difference was statistically significant.In terms of ≥grade Ⅲ adverse events,the experiment group had higher rates of rash ［OR=1.64,95%CI(1.20，2.24),P=0.002］,hypertension ［OR=6.50,95%CI(4.07，10.39),P<0.000 01］,proteinuria ［OR=9.87,95%CI(2.97，32.81),P=0.000 2］.There was no significant difference in diarrhea ［OR=1.09,95%CI(0.54，2.17),P=0.82］,and hemorrhage ［OR=1.74,95%CI(0.74，4.09),P=0.21］ between two groups.Conclusion:The treatment of EGFR-TKIs plus Bevacizumab in patients with non-small cell lung cancer can improve median progression-free survival,objective response rate,disease control rate.However,this program lead to increased incidence of adverse events such as rash,hypertension,proteinuria.