Characteristics And Survival In Non-small Cell Lung Cancer Patients Harbored Primary And Acquired EGFR T790M Mutation

Background: The identification of epidermal growth factor receptor(EGFR)and development of EGFR tyrosine kinase inhibitors(TKIs)brought a new sight and therapy for non-small cell lung cancer(NSCLC),patients could achieve a median progression-free survival(PFS)of 10 months,however,resistance inevitably developed.T790 M had been confirmed as the major mechanism.In addition,Primary epidermal growth factor receptor(EGFR)T790M mutation can be occasionally identified in previous TKIsuntreated NSCLC patients with the popularization of EGFR detection.Osimertinb was approved to be the standard therapy for patients with acquired EGFR-T790 M.However,the studies efficiency of osimertinib in real word and primary EGFR-T790 M are rare.Methods: To analysis clinical characteristics and outcomes in patients with primary and acquired EGFR T790 M mutation;To explore the efficiency of osimertinib in primary and acquired EGFR T790 M mutation;To summary the survival differences.We respectively collected the data of patients diagnosed with EGFR mutation from 2012 to 2017 in Shanghai Chest Hospital.Results:(1)From Jan 2012 to Sep 2017,a total of 246 patients diagnosed with acquired EGFRT790 M mutation and have enough survival and treatment data to analysis.The median progression free survival(PFS)was 12.0 months,the median overall survival(OS)was 54.37 months.(2)The median PFS of patients harbored EGFR 19del/20T790 M was 12.97 months,which was longer than 9.73 months in patients harbored EGFR 21L858R/20T790 M,P=0.032.In COX model,the HR was 0.66,95% CI: 0.47-0.94,P=0.019.The OS from Osimertinib is 23.33 months in patients with EGFR 19del/20T790 M,longer than that in patients with EGFR 21L858R/20T790 M,21.27 months,P=0.023。The median OS of patients harbored EGFR 19del/20T790 M was 55.97 months,the patients harbored EGFR 21L858 R /20T790 M was 46.67 months,however,the P value didn’t reach 0.05.(3)From Jan 2012 to Oct 2017,EGFR mutation could be detected in 6934 patients.Primary EGFR T790 M mutation could be detected in 112(1.62%)patients.Of 112 patients,98 cases were adenocarcinoma,2 cases were squamous cell carcinoma,1 case was adeno-squamous carcinoma.38 cases received 1st generation TKIs,the median PFS was 2.0 month,27 cases received osimertinib,the median PFS was 16.0 months.(4)From Jan 2012 to Jan 2017,18 patients harbored primary EGFR-T790 M mutation and 72 patients harbored acquired EGFR-T790 M mutation received osimertinib,the median PFS was 17.0 months and 10.0 months,respectively,P=0.022,the OS was 29.9 months and 50.4 months,respectively,P=0.016.Conclusions: EGFR T790 M mutation always coexists with other sensitive EGFR mutations.Primary T790 M mutation is likely to coexist with 21L858 r R,while acquired with 19 del.Both showed good response to osimertinib treatment,whereas patients with primary T790 M mutation could benefit more.However,patients with acquired T790 M mutation have had better overall survival at any time during the clinical treatment.