第三代EGFR-TKI在局部晚期/晚期非小细胞肺癌一线治疗的有效性和安全性网状Meta分析

Evaluate the Efficacy and Safety of the Third-generation EGFR-TKI as First-line Treatment for Locally Advanced/advanced Non-small Cell Lung Cancer by a Network Meta-analysis

目的表皮因子受体酪氨酸激酶抑制剂(Epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKI)是非小细胞肺癌(Non-small cell lung cancer,NSCLC)一线治疗的主要选择,第3代TKI是已上市最新的EGFR-TKI药物。本研究的网状Meta分析(Network meta-analysis,NMA)对比第3代TKI和标准EGFR-TKI治疗(Standard-of-care EGFR-TKI,SOC)之间有效性和安全性。方法系统检索PubMed、Embase、The Cochrane Library、The Web of Science、中国知网(CNKI)等数据库关于第3代TKI一线治疗晚期NSCLC的随机对照试验(randomized controlled trial,RCT)(截至2023年04月04日)。RevMan 5.3进行质量评估,使用R(版本4.2.0)统计学分析。结果共纳入5项RCT,共计1,800名患者。与SOC相比,患者的无进展生存期(Progression-free survival,PFS)在第3代TKI中明显延长(HR=0.44~0.50,P<0.05),其中伏美替尼(Furmonertinib,Fur)提示较上级。在疾病控制率(Disease control rate,DCR)中奥希替尼(Osimertinib,Osi)提示较上级;Fur在3级以上不良反应发生率(Grade 3 or above adverse events,≥3AE)和严重不良反应发生率(Serious adverse events,SAE)中提示较低不良反应风险。于PFS进行人群分析,在小于65岁(男性/无脑转移/ECOG评分0/ECOG评分1/Ex19del突变)患者中,Fur的排序第一。结论本研究结果显示,Fur一线治疗NSCLC的优于其它第3代TKI。

OBJECTIVE Epidermal factor receptor-tyrosine kinase inhibitors(EGFR-TKI)are the main first-line treatment for non-small cell lung cancer(NSCLC).The third-generation TKI is the latest EGFR-TKI drugs that have been marketed.This study conducted a network Meta-analysis(NMA)to compare the efficacy and safety of third-generation TKI versus Standard-of-care EGFR-TKI(SOC).METHODS PubMed,Embase,The Cochrane Library,The Web of Science,China National Knowledge Infrastructure(CNKI)and other databases were searched for randomized controlled trials(RCTs)of third-generation TKI as first-line treatment for advanced NSCLC(up to April 04,2023).RevMan 5.3 was used for quality assessment,and R(version 4.2.0)was used for statistical analysis.RESULTS 5 RCTs involving 1,800 patients were included.Compared with SOC,the progression-free survival(PFS)was significantly prolonged in third-generation TKI(HR=0.44-0.51,P<0.05),and Furmonertinib(Fur)was superior.Osimertinib(Osi)was superior to osimertinib in disease control rate(DCR).Fur showed a lower risk of adverse events in terms of the incidence of grade 3 or above adverse events(≥3AE)and the incidence of serious adverse events(SAE).In PFS,Fur ranked first in patients younger than 65 years(male/no brain metastasis/ECOG score 0/ECOG score 1/Ex19del mutation).CONCLUSION The results of this study showed that Fur was superior to other third-generation TKIs in the first-line treatment of NSCLC.