Meta-analysis Of EGFR-TKIs In EGFR-mutant Non-small Cell Lung Cancer Patients And Clinical Retrospective Validation

Objective: Nowadays,Targeted therapy has become an indispensable means for the treatment of advanced non-small cell lung cancer(NSCLC).Epithelial growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)can significantly prolong the survival of patients with advanced lung cancer carrying EGFR gene mutation.There are clinical studies suggesting that there is a significant correlation between the effects of targeted drugs on the treatment of gene mutation types.This study aims to explore the relationship between the two most common EGFR mutations,the exon 19 deletion and the L858 R mutation.In this study,we used Meta-analysis to evaluate the therapeutic effects of EGFR-TKIs on exon 19 deletion mutation and exon 21 L858 R gene mutation among overall survival(OS),progression free survival(PFS),objective response rate(ORR)and disease control rate(DCR).At the same time,the clinical data of the hospital were collected to explore the difference in efficacy of different mutation subtypes of EGFR to provide a theoretical basis for clinical guidance and guide the prognosis.Methods:(1)Comprehensive search of Pubmed database,Embase and Meadline database,Cochrane library,China National Knowledge Infrastructure,Chongqing Weipu database,Wanfang database are six authoritative databases at domestic and foreign,the search period is from January2008 to September 2018.Screened out the first-line and mixed-line clinical studies comparing the efficacy of EGFR-TKIs on exon 19 deletion mutation and exon 21 L858 R gene mutation.The literature screening was carried out strictly according to the inclusion and exclusion criteria,using stata12.0 software for Meta-analysis of extracted data.(2)From January 2011 to December 2016,a total of 226 patients with advanced non-small cell lung cancer(NSCLC)with EGFR positive gene mutation were collected from Xinjiang Uygur cancer hospital.Retrospectively analyze the correlation between the clinical characteristics of the two groups,and compare the difference in the efficacy of targeted therapy,and analyze the correlation between clinical characteristics and PFS,OS.The statistical software SPSS24.0 version was used for data processing and statistical analysis.Results:(1)This Meta-analysis finally included 38 studies,a total of 3408 patients.The results of Meta analysis showed that the differences of PFS[HR=0.75,95% CI(0.65,0.86),P<0.0001]and OS[HR=0.77,95% CI(0.64,0.92),P=0.004] between the first-line targeted treatment deletion mutation group and the 21 L858 R mutation group were statistically significant;And the difference of PFS[HR=0.65,95%CI(0.47,0.91),P =0.011] and OS [HR=0.66,95%CI(0.46,0.95),P=0.024] between the first-line targeted treatment deletion mutation group and the 21 L858 R mutation group were statistically significant.(2)A retrospective analysis of 226 eligible patients,the distribution frequency of the two gene mutation types in clinical characteristics was not statistically significant(P>0.05);the results of univariate and multivariate analysis showed that the PFS of patients with first-line targeted therapy was significantly correlated with the type ofgene mutation,and the median PFS of mutation 19 and mutation 21 L858 R were 13.5 months[95%CI(7.4,16.6)] and 11.7 months [95%CI(10.0,13.4)],P=0.038;the results of second and third line targeted therapy showed that PFS was significantly related to gene mutation type,the median PFS of 19 mutation and 21 L858 R were 16.0 months [95%CI(11.0,20.9)] and 11.0months [95%CI(7.3,14.7)],P=0.041,respectively.Conclusion: The survival time of EGFR-TKIs patients with exon 19 deletion mutation in the first line and mixed line treatment may be longer than that of L858 R gene mutation in exon 21,which suggests that EGFR mutation state may have different prognostic prediction effect.EGFR19 exon deletion mutation is an important index for predicting EGFR-TKIs in NSCLC patients.