奥希替尼与第一、二代EGFR-TKIs治疗EGFR突变晚期非小细胞肺癌疗效及安全性的Meta分析

A Meta-analysis of osimertinib or first and second-generation EGFR-TKIs in patients with EGFR-mutated advanced non-small cell lung cancer

目的系统评价奥希替尼与第一、二代表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)治疗EGFR突变晚期非小细胞肺癌(NSCLC)的疗效及安全性。方法计算机检索PubMed、Embase、The Cochrane Library、Web of Science、中国知网和万方等数据库中截至2020年2月所有使用奥希替尼对比其他EGFR-TKIs治疗EGFR突变的晚期NSCLC患者的随机对照试验(RCT)。根据Cochrane质量评价手册的质量评价标准评价纳入的RCT的质量,采用RevMan 5.3软件进行统计学分析。主要的研究终点是无进展生存期(PFS),次要研究终点是客观缓解率(ORR)、疾病控制率(DCR)和不良反应。结果最终纳入3个RCT,共804例患者。Meta分析结果显示,与第一、二代EGFR-TKIs相比,奥希替尼治疗延长了EGFR突变晚期NSCLC患者的中位PFS(HR=0.48,95%CI=0.40~0.58,P<0.00001),提高了DCR(OR=1.05,95%CI=1.01~1.10,P=0.01),但在ORR方面2组间差异无统计学意义(OR=1.10,95%CI=0.93~1.31,P=0.27)。不良反应方面,奥希替尼拥有更低的3级以上不良事件(AEs)发生率(RR=0.75,95%CI=0.63~0.88,P=0.0008)。结论奥希替尼治疗EGFR突变晚期NSCLC患者可以提高中位PFS和DCR,并且拥有更低的3级以上AEs发生率。

AIM To evaluate the effectiveness and safety of osimertinib and first and second-generation epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs)in the treatment of EGFR-mutated advanced non-small cell lung cancer(NSCLC).METHODS PubMed,Embase,The Cochrane Library,Web of Science,CNKI and Wanfang Data were electronically searched to collect randomized controlled trials(RCTs)of osimertinib and first and second-generation EGFR-TKIs in the treatment of EGFR-mutated advanced NSCLC.The search time ranged from inception to February,2020.Methodological quality of the selected trials was evaluated according to the Cochrane handbook,and Meta analysis was utilized with RevMan 5.3 software.The main outcome of included studies was progression-free survival(PFS)and the secondary outcomes were disease control rate(DCR),objective response rate(ORR)and adverse drug reactions.RESULTS Three RCTs,totally of 804 patients,were identified and included in present study.Meta-analysis showed that osimertinib treatment could improve the median PFS(HR=0.48,95%CI=0.40-0.58,P<0.00001),DCR(OR=1.05,95%CI=1.01-1.10,P=0.01)compared with first and second-generation EGFR-TKIs.However,there was no significant difference in ORR between the 2 groups(OR=1.10,95%CI=0.93-1.31,P=0.27).In term of adverse drug reactions,osimertinib has a lower rate of≥grade 3 adverse events(RR=0.75,95%CI=0.63-0.88,P=0.0008).CONCLUSION Osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer can improve the median PFS and DCR and has a lower rate of≥grade 3 adverse events.