The Prognostic Factors Associated With EGFR-TKI Efficacy In NSCLC Patents With EGFR Mutations

BackgroundTyrosine kinase inhibitors(TKIs)are clinically effective in non-small cell lung cancer(NSCLC)patients who have epidermal growth factor receptor(EGFR)oncogene mutations.However,some patients with EGFR mutant NSCLC do poorly after an initial response to EGFR TKIs,whereas others can have prolonged lives despite advanced disease.In this study,we sought to identify genetic parameters associated with variable clinical outcome by analyzing EGFR mutant NSCLC patients who were treated with EGFR TKIs.MethodsA total of 71 patients who had metastatic or recurrent NSCLC with activating EGFR mutation treated first generation TKI retrospectively reviewed.The PFS of these patients were either longer than 24months or shorter than 6 months.Specimens before TKI treatments were collected.Next generation sequencing of 416 gene panel was performed to identify genetic differences between groups.TMB was also calculated.ResultsSensitive EGFR mutations of 19del or 21L858R were detected by NGS in all patients;the 21L858R mutation was the major type.The most frequent accompanying somatic mutations were TP53,RB1,MAP2K2 and BIM polymorphism.Among them,TP53 mutation sites were different between groups.And MAP2K2 were found only in long PFS group.The incidences of BIM polymorphism were not significantely different between groups.Co-occuring of driver mutations including T790M,MET amplification,BRAF V600E,and ALK fusion were more often seen in short PFS group(P=0.018).Tumor mutation burdens(TMB)were low in both groups.The patients trended to have higher TMB in short PFS group.But the differences were not significant.ConclusionCo-occuring driver gene mutations were negative predictive factors of TKI therapy in EGFR-mutated patients.NGS which chould give more genetic informations of patients might be a useful tool in predicting efficacy in TKI treatment.