Effect Of Secondary T790M Mutation On Advanced Non-small Cell Lung Cancer And Prognostic Factors

Objective: Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors(EGFR-TKIs)have a good treatment for patients with advanced non-small cell lung cancer(NSCLC)with EGFR mutations effect.However,almost all patients in the application of EGFR-TKIs treatment process will face the problem of drug resistance,the most common drug resistance mechanism is T790M mutation.This study was to investigate the relationship between T790M gene mutation and EGFR-TKIs secondary resistance and prognosis in patients with advanced lung adenocarcinoma,so as to provide a theoretical basis for the follow-up treatment regimen.Methods:1 A total of 19 patients with advanced lung adenocarcinoma who were diagnosed by histopathology and / or cytology were enrolled in this study.All patients had EGFR gene(18,19 or 21)mutations and were treated with gefitinib,erlotinib or erlotinib.After the progression of the disease,the EGFR gene mutation was detected in the patient.Results The patients were divided into two groups: T790M mutation group and no T790M mutation group.The T790M mutant group was followed by treatment with oxetidine for the presence of T790M mutant followed by chemotherapy or a targeted drug other than otcitidine.After one month of application,the efficacy of the two groups was evaluated according to the evaluation criteria of the efficacy of RECIST1.1 solid tumor.The objective response rate(ORR),disease control rate(IDR)DCR),Progression Free Survival(PFS),Total Survival(OS).At the same time,according to age,gender,physical status(PS)score,treatment history(primary history of surgery,history of chemotherapy),with or without chronic diseases(hypertension,coronary heart disease,thrombosis),metastatic organs and other aspects Single factor and multivariate analysis to find the factors that affect the efficacy.2 Follow-up by telephone,to collect hospital or outpatient visits.The follow-up period was calculated from the first day after the patient was admitted,with the deadline of January 31,2017.As of the follow-up date,9 out of 19 patients died,0 were lost,follow-up rate: 100%.Patient treatment began as the starting point for the study,the end of the last follow-up time,lost,the patient died time.3 SPSS 21.0 statistical software was used for statistical analysis.The count data were analyzed by χ2 test.The survival curve was drawn by Kaplan-Meier method.The influencing factors of OS were analyzed by Cox regression analysis.The data were analyzed by P <0.05.Results:1 The status of T790M in patients with acquired EGFR-TKIs resistant NSCLCEGFR mutations were observed in 9 patients after treatment: 4 patients with EGFR 19 combined with T790M mutation,5 patients with EGFR 21 with T790M mutation,3 patients with T790M mutation,7 patients without T790M mutation(with no other EGFR Gene mutation).Among them,T790M mutation was detected in peripheral blood of 12 patients,accounting for 63.15% of the total subjects.2 Acquired EGFR-TKIs-resistant NSCLC patients with follow-up treatment optionsOf the 19 patients enrolled,12 of the T790M mutant patients were treated with oxetidine,followed by 7 patients without T790M mutations,and 5 patients received other targeted drugs other than ocitinib Tebufi,erlotinib or erlitinib),and 2 patients were treated with docetaxel-containing regimens.3 The prevalence of DCR and ORR in patients with acquired EGFR-TKIs-resistant NSCLC after different treatmentsThe DCR of the T790M mutant was 50.0%(6/12),and the DCR of the T790M mutant was 57.1%(4/7).There was no significant difference in the disease control rate between the two groups(P = 0.764).The ORR of both groups was 0.4 The prevalence of PFS and OS in patients with acquired EGFR-TKIsresistant NSCLC after different treatmentsOf the 19 patients enrolled,12 patients received data from PFS,including 8 patients with T790M mutations and 4 patients without T790M mutations.The median PFS of the T790M mutation group was 4 months,the 95% confidence interval was [3.105,4.895],the median PFS in the T790M mutation group was 3 months,the 95% confidence interval was [1.503,4.497],P = 0.486,No statistically significant difference.All patients were included in OS statistics.The median OS was 31 months in the T790M mutant group,95% confidence interval was [22.423,39.577],26 months in the absence of T790M mutant,95% confidence interval(10.728,41.272),P = 0.044,there was a statistically significant difference.5 Factors influencing the prognosis of patients with acquired EGFR-TKIs resistant NSCLCAll patients were included in the prognostic analysis,the results for the prognostic factors,including: age,gender,PS score,with or without primary tumor surgery,with or without vascular targeting drugs,serum CEA levels,with or without chemotherapy history,with or without bone Metastasis,with or without brain metastases,with or without malignant pleural effusion,with or without lung metastasis,with or without lymph node metastasis,coagulation function,with or without hypertension,with or without heart disease,whether there is a single factor analysis of thrombosis and found that patients with or without heart disease Thrombosis was associated with OS(P <0.05).Multivariate analysis of single-factor analysis of P <0.05 showed that the presence or absence of thrombosis was independent of OSR-TKIs-resistant patients with NSCLC(P <0.05).Conclusions:1 T790M mutations are the most frequently occurring drug-resistant mutations in patients with advanced non-small cell lung cancer after EGFR-TKIs treatment.2 The mutation of EGFR gene in patients with advanced non-small cell lung cancer can be dynamically monitored by peripheral blood,and the mutation of T790M gene can be detected in time to provide the theoretical basis for follow-up treatment.3 In patients with advanced EGFR-TKIs-resistant advanced non-small cell lung cancer,the OS of the T790M mutation was significantly prolonged by treatment with ochitinib after treatment with non-T790M mutations treated by chemotherapy or non-ototinib.4 For patients with advanced non-small cell lung cancer after EGFRTKIs resistance,whether the presence of heart disease,the presence of thrombus is an independent factor in OS.