EGFR-TKIs一线治疗晚期非小细胞肺癌的有效性和安全性比较:网状Meta分析

Comparative efficacy and safety of first-line EGFR-TKIs for advanced non-small cell lung cancer:a network meta-analysis

目的比较吉非替尼、厄洛替尼和阿法替尼一线治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的有效性和安全性。方法系统检索2008年12月-2018年12月收录在PubMed、EMBASE和The Cochrane Library中的相关文献进行贝叶斯网状meta分析。结果共纳入10篇文献,包含2 275名患者。就有效性而言,累积排序概率图下面积(surface under the cumulative ranking,SUCRA)显示厄洛替尼在无进展生存期(progression-free survival,PFS)方面最佳(0.88),阿法替尼在客观反应率(objective response rate,ORR)(0.82)和疾病控制率(disease control rate,DCR)(0.86)方面最佳,吉非替尼在PFS(0.45),ORR(0.42)和DCR(0.45)方面均最差。就安全性而言,仅厄洛替尼与含铂的双重化疗在3~4级不良反应率(OR=0.29,95%CI:0.08~0.98)和停药率(OR=0.14,95%CI:0.01~0.86)方面的差异有统计学意义。排序结果也支持厄洛替尼的安全性最好。SUCRA结果提示吉非替尼(0.31)发生3~4级不良反应的可能性比阿法替尼(0.57)小,其(0.44)发生停药的可能性与阿法替尼(0.41)相似。结论厄洛替尼可能是三者中一线治疗晚期NSCLC的首选药物。

Objective To compare the efficacy and safety of gefitinib,erlotinib,and afatinib in the first-line treatment of advanced non-small cell lung cancer(NSCLC).Methods PubMed,EMBASE,and The Cochrane Library were searched to identify the relevant literatures published from December 2008 to December 2018.Bayesian network meta-analysis was carried out to rank the three treatments.Results A total of ten eligible studies involving 2275 patients were enrolled.In terms of efficacy,the surface under the cumulative ranking(SUCRA)indicated that erlotinib performed best in progression-free survival(PFS)(0.88),afatinib performed best in objective response rate(ORR)(0.82)and disease control rate(DCR)(0.86),gefitinib performed worst in PFS(0.45),ORR(0.42),and DCR(0.45).For safety,the differences of grade 3 or 4 adverse events rate(OR=0.29,95%CI:0.08-0.98)and discontinuation rate(OR=0.14,95%CI:0.01-0.8)between erlotinib and the platinum-based doublet chemotherapy were statistically significant.The ranking results also supported that erlotinib was the safest.SUCRA results suggested that gefitinib(0.31)had a lower grade 3 or 4 adverse events rate than afatinib(0.57),and the possibility of discontinuation in gefitinib(0.44)was similar to that of afatinib(0.41).Conclusion Erlotinib might be the preferred first-line treatment for advanced NSCLC after weighing and balancing the benefits and risks.