Predictive Role Of Pretreatment EGFR T790M Mutation On TKI Therapy In NSCLC Patients-a Meta-analysis

Background and PurposeT790M mutation is the main reason for resistance in non-small-cell lung cancer(NSCLC) patients with epidermal growth factor receptor (EGFR) sensitive mutation undertyrosine kinase inhibitor (TKI) treatment. Although initially found as a resistance gene,recently more and more studies have confirmed T790M mutation in TKI naive NSCLCpatients with EGFR sensitive mutation, which means these patients have both sensitiveand T790M mutation before EGFR-TKI treatment. Coming along with the improvementof detection method, both in sensitivity and accuracy, the detected positive ratio of T790Mmutation comes out much higher. Although current guidelines all recommend TKI asfirst-line therapy in advanced NSCLC patients with sensitive EGFR mutation, the role ofpretreatment T790M mutation on these patients with EGFR-TKI therapy is not clearly yet.The purpose of the current study is to analyze the role of pretreatment T790M on NSCLCpatients with EGFR sensitive mutation having TKI treatment.Material and MethodThe study uses meta-analysis as the main method to pool the studies focusing on therole of pretreatment T790M in patients with EGFR sensitive mutation accepting TKItreatment. By extracting the hazard ration (HR) and its95%confidence intervals (CI) ofpretreatment on the PFS of TKI therapy in individual studies, the study uses random effect model and fixed effect model to combine，calculate and analyze.ResultsThis study picks5articles from a total of372articles, with a total of299patients. Allthe patients involved have EGFR sensitive mutation, and the pretreatment T790Mmutation rate is47.5%(142/299), ranging from34.9%to80%. Analysis on the299casesshows T790M mutation has negative predictive effect on TKI treated PFS, with a HR of2.366(95%CI[1.011-6.695]), and heterogeneity is significant among the selected studies.While after deleting rare EGFR sensitive mutation and non-first-line TKI cases, analysison277cases left shows the HR of T790M mutation on TKI treated PFS is1.888(95%CI[1.574-2.265]), and there is no significant heterogeneity among the selected studies.There is no significant publication bias as well.ConclusionThis meta-analysis found out TKI naive patients with both EGFR sensitive mutationand T790M mutation have shorter PFS than those with only EGFR sensitive mutationwhen treated with TKI, and the difference is significant.