Analysis Of Clinical Characteristics Of Advanced Lung Adenocarcinoma Patients With Acquired T790M Mutation In The Epidermal Growth Factor Receptor

Objective: Epidermal growth factor receptor(EGFR)gene is one of the common driver genes of non-small cell lung cancer(NSCLC).The first and second generation EGFR-tyrosine kinase inhibitor(EGFR-TKI)showed significant efficacy but generally acquired drug resistance after a period of treatment.It has been reported that acquired T790M mutation in EGFR is one of the common mechanisms underlying the development of EGFR-TKI resistance.The third generation EGFR-TKI has a significant beneficial effect on advanced NSCLC with T790M mutation.Therefore,it is necessary to detect the T790M mutation in EGFR-TKI resistant patients.The purpose of this study was to investigate the T790M mutation rate and the relationship between different clinical features and T790M mutation frequency in first-generation and second-generation EGFR-TKI first-line treatment of lung adenocarcinoma patients with drug resistance,to try to find the high-risk clinical factors of acquired T790M mutation,and to compare the difference in prognosis between T790M mutation positive patients and T790M mutation negative patients.Methods: Data of 220 patients were collected between September 2018 to December 2020 in the Department of respiratory and critical care medicine of the first affiliated hospital of Wannan Medical College.These patients were pathology diagnosed with lung adenocarcinoma,TNM stage IIIB/IV,and received fist line treatment with the first generation and second generation of EGFR-TKI and subsequently developed disease progression after treatment,and then performed EGFR genetic testing.Among these patients,61 cases(27.8%)had the T790M mutation,159 cases(72.2%)did not have the T790M mutation.Among 61 T790M positive cases,42 cases with relatively complete clinical data were selected as the experimental group,and 50 cases from the 159 T790M negative cases were selected as control group.Clinical and pathological data of enrolled patients were recorded,including gender,age,smoking history,clinical stage,ECOG score,initial EGFR mutation subtypes,brain metastasis,duration of TKI treatment,the type of EGFR-TKI used and the initial EGFR-TKI efficacy.Kaplan-Meier survival curve was used to analyze the relationship between T790M mutation and patient prognosis in combination with the follow-up data of enrolled patients.Results:Among the 92 enrolled patients,36(39.1%)were males and 56(60.9%)were females.Eighty patients(87.0%)received first-generation EGFR-TKI,among which 43patients(46.7%)received gefitinib,26 patients(28.3%)received erlotinib,11 patients(12.0%)received ectinib,and 12 patients(13.0%)received second-generation EGFR-TKI atinib.For the initial EGFR mutation subtypes,50(54.3%)of the 92 enrolled patients had 19 exon deletion mutation(19del),33(35.9%)had 21 exon L858R point mutation(21L858R),and 9(9.8%)had mixed mutation(2 19del+21L858R,3 21L858R+S768I,and 4 21L858R+20-Ins).The T790M mutation was found in 30(60.0%)of 50 patients with initial 19del mutation,11(33.3%)of 33 patients had 21L858R mutation,and 1(11.1%)of 9 patients had mixed mutations.The positive rate of T790M mutation in patients with initial 19del mutation was significantly higher than that in patients with 21L858R and mixed mutations(P=0.005).The T790M mutation rate was 29.4%(10/34)in patients receiving their initial EGFR-TKI treatment for less than 12 months in 34 out of 92 patients(36.9%)and the T790M mutation rate was 57.4%(31/54)in patients receiving their initial EGFR-TKI treatment for 12 to 24months in 54 out of 92 patients(58.7%).The T790M mutation rate was 25.0%(1/4)in patients receiving their initial EGFR-TKI treatment for>24 months in 4 out of 92 patients(4.4%).The difference between T790M mutation and initial EGFR-TKI treatment time>12 months was statistically significant(P<0.05).There was no statistical significance between T790M mutation and gender,age,smoking history,clinical stage,ECOG score,brain metastasis,initial TKI efficacy and EGFR-TKI type(P>0.05).In terms of patient prognosis,the median PFS was12.1 months in the T790M mutation-positive group and 9.0 months in the T790M mutation-negative group,and the difference was statistically significant(P<0.001).Therefore,PFS of acquired T790M mutation-positive patients were longer than those of T790M mutation-negative patients.Conclusion:In lung adenocarcinoma patients that developed drug resistance to the first generation and second generation EGFR-TKI therapy the positive rate of T790M mutation is closely related to both EGFR 19Del and if the treatment duration is longer than 12 months.On the other hand,the clinical characteristics of gender,age,smoking history,clinical stage,ECOG score,brain metastases,initial TKI curative effect,EGFR-TKI types are not significant correlated with the T790M mutation rate.Drug-resistant lung adenocarcinoma patients with acquired T790M mutation who received first-generation and second-generation EGFR-TKI in first-line treatment may have better PFS and long-term survival.