Clinical Efficacy Of Chemotherapy Followed By Gefitinib In Advanced Lung Adenocarcinoma With EGFR Mutation

Background and ObjectiveWith the advancement of society,the improvement of medical diagnostic,the extension of life expectancy and changes in diet structure,the incidence of malignant tumors has a tendency of increasing.The morbidity and mortality of lung cancer are the highest in all cancer,which bitterly threatens human health.Because the early symptoms about lung cancer were not obvious,most patients were already in advanced stage or had distant organ metastasis when they are diagnosed,then they will lose the opportunity of surgery and have to receive chemotherapy.Due to the cytotoxic effect and low objective response rate of traditional chemotherapeutic drugs,the treatment of advanced lung cancer was in the plateau stage.With the improvement of molecular detection technology,especially the discovery of the EGFR(Epidermal growth factor receptor)gene,and the development of targeted drugs,various large clinical trials have confirmed that gefitinib has obvious survival benefits compared with traditional chemotherapy for advanced non-small cell lung cancer(NSCLC).Because of the good tolerance and weak side effects have quickly made gefitinib as the standard treatment for advanced non-small cell lung cancer with EGFR sensitive mutation.But oral targeted drugs have limited benefit time,and will have unavoidable acquired drug resistance in the later treatment,which limits the long-term survival of advanced patients.Due to the different mechanisms of molecular targeted drugs and cytotoxic drugs,how to combine traditional chemotherapy with molecular targeted drugs has became a controversial question in the treatment of advanced lung adenocarcinoma,in order to delay the occurrence of drug resistance.This project retrospectively analyzed the clinical effect and safety of gefitinib followed by chemotherapy in advanced lung adenocarcinoma with sensitive mutations,through a large sample case-control study.Masterials and methodsWe collect 8796 newly diagnosed lung adenocarcinoma patients,who were consecutively admitted to the First Affiliated Hospital of Zhengzhou University between January 2015 and January 2018.All patients were diagnosed with adenocarcinoma by pathological biopsy.Patients with EGFR exon 19 and exon 21 L858R mutation were selected.1.According to different treatment regimen,121 patients were set as the control group recepted gefitinib alone,93 received chemotherapy and gefitinib maintenance,which were set as the observation group.According to the results of normality test and homogeneity test of variance,quantify clinical data between the two treatment groups use two independent sample t-tests or rank sum tests,qualitative data use Chi-square test.2.Statistics of progress free survival(PFS)and overall survival(OS)between the two groups,Comparison of survival data between the two groups using Kaplan-Meiermrethod,log-rank is used to compare the difference in survival between the two groups.3.General clinical data that may be affected patients' PFS or OS,we get univariate and multivariate analysis by using COX regression models.4.Adverse reactions were compared between the two treatment groups by using Chi-square test,Grade 3 adverse reactions or obove between the two groups were analysed by Chi-square continuous correction method and Fisher's exact probability method.The above statistical analysis is processed by SPSS22.0 statistical software,With?=0.05 as the inspection level,?<0.05 is considered statistically significant.Results1.Remission rate:In the observation group,0 cases were CR,40 cases were PR,43 cases were SD,and 10 cases were PD.The disease control rate(DCR)was 89.2%,and the objective response rate(ORR)was 43.0%.In the control group,0 cases were CR,34 cases were PR,73 cases were SD,and 14 cases were PD.The disease control rate was 88.4%and the objective response rate was 28.1%.The disease control rate was not statistically significant between the two groups(P>0.05),and the objective response rate was significantly different between two groups(P<0.05).2.Survival analysis:The median PFS in the observation group was 15 months,the median OS was 52 months.The median PFS in the control group was 9 months,and the median OS was 36 months.The difference between the two groups was statistically significant(P<0.05).3.Univariate and multivariate analysis:Genetic mutation type is an independent influencing factor for PFS,and EGFR exon 19 mutation is a protective factor in prolonging patients' PFS(HR=0.688,95%CI 0.538-0.879,P=0.003).4.According to subgroup analysis,regardless of exon 19 mutation or exon 21 L858R mutation,the difference in PFS between the two groups was statistically significant(P<0.05).5.Adverse reactions:Common adverse reactions in the observation group were gastrointestinal reactions(40.9%)and bone marrow suppression(62.3%).Common adverse reactions in the control group were rash(12.4%)and gastrointestinal reactions(12.4%).There were statistically significant differences between the groups about bone marrow suppression,gastrointestinal reactions,liver and kidney function damage(P<0.05),but there were no significant differences between the groups of Grade 3 adverse reactions or obove(P>0.05).ConclusionChemotherapy followed by Gefitinib maintenance therapy in advanced lung adenocarcinoma with EGFR-sensitive mutation can achieve better clinical efficacy.Under conditions where the adverse reactions can be tolerated and controlled,significantly prolongs patients' PFS and OS and delays the occurrence of gefitinib resistance,especially in patients with EGFR exon 19 mutations,the effect is particularly significant.