Analysis Of EGFR T790M Mutation Rate And Related Characteristics After First-line Treatment Of Advanced Non-small Cell Lung Cancer With Sensitive Mutations

Objective:This study is to analyze the relationship between T790M mutation and clinical characteristics after the failure of first-line tyrosine kinase inhibitors in the treatment of epidermal growth factor receptor mutation in advanced non-small cell lung cancer.Explore the clinical predictors of EGFR T790M mutation,screen mutation advantage populations,and further guide clinical treatment.Methods:Using a retrospective analysis method,we collected 2302patients with stage IIIB-IV non-small cell lung cancer treated and treated by our hospital from August 2013 to September 2019 in the Forth Hospital of Hebei Medical University.Screen patients who meet the inclusion criteria and collect basic clinical and pathological data of patients,including gender,age of enrollment,smoking status,stage,pathological type,metastasis site,initial biopsy method,initial genetic test specimen,baseline gene mutation status,first-line epidermal growth factor receptor tyrosine kinase inhibitors,progression-free survival of first-line treatment,the best response during the first-line treatment,the progress site after the first-line treatment,the biopsy method after the progress,and the presence or absence of the T790M mutation after the progress.SPSS21.0 statistical software was used for analysis,and the relationship between T790M mutation and clinical characteristics is analyzed by chi-square test.For statistically significant clinical characteristics,logistic regression model was used for multivariate analysis.The relationship between PFS and clinical characteristics is analyzed by Kaplan-Meier survival.Factors that may affect PFS are included in the COX multivariate analysis.P<0.05has statistically significant.Results:1. A total of 167 patients are included,and the T790M mutation rate is52.7%(88/167);2. In univariate analysis,the effect of median PFS in first-line treatment on T790M mutations is statistically significant.Patients with PFS>12 months are more likely to have secondary T790M mutations(odds ratio,1.921;95%CI,1.038-3.556;P=0.038),but doesn't reach statistical significance in multivariate analysis(adjusted odds ratio,1.667;95%CI,0.815-3.409;P=0.161);3. In logistic regression analysis of the progression mode,intracranialprogression is statistically significant in both univariate analysis and multivariate analysis(adjusted odds ratio,0.070;95%CI,0.006-0.851;P=0.037),and the progression mode is intracranial progressive patients do not easy to acquire secondary T790M mutation.The intracranial progression mode after treatment failure can be used as an independent factor affecting secondary T790M mutation;4. The best response during treatment is that patients with partial responseare prone to secondary T790M mutation,which is also an independent influencing factor of T790M mutation(adjusted odds ratio,2.548;95%CI,1.236-5.253;P=0.011);5. In the prognostic analysis of first-line targeted therapy,the median PFS of first-line therapy for secondary T790M positive and negative groups is 13.6months and 10.9 months respectively(X~2=5.148,Log rank P=0.023);The median PFS in the PR group is 14.0 months and the median PFS in stable disease group is 10.1 months(X~2=10.445,Log rank P=0.001).In the COX multivariate analysis,the best response(P=0.001)and the secondary T790M mutation(P=0.045)all reaches statistical significance.Both of them are significantly related to the prognosis of advanced non-small cell lung cancer and are independent risk factors affecting the prognosis of patients with advanced non-small cell lung cancer.Conclusions:1.The Secondary T790M mutation rate in this study is 52.7%.The occurrence of secondary T790M mutation is related to the best response during EGFR-TKI treatment,the site of treatment failure(intracranial progression),and median PFS.Among them,the best response and intracranial progression are independent factors that affect the mutation of T790M.2.In prognostic analysis,those with the best response is PR and secondary T790M positive mutations has longer PFS during the first-line EGFR-TKI treatment,which are independent risk factors affecting the prognosis of patients with advanced non-small cell lung cancer.