Analysis Of EGFR Gene Mutation Status In Patients With Advanced Lung Adenocarcinoma After First-line EGFR-TKIs Targeted Therapy And Its Relationship With Efficacy And Prognosis

Objective: There are few studies on the relationship between different EGFR gene mutation status and efficacy and prognosis after first-line epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)treatment.In this study,patients with EGFR-sensitive mutations in advanced lung adenocarcinoma were selected as the research objects,aiming to compare the effects of different EGFR gene mutation states on the efficacy and prognosis after first-line EGFR-TKIs targeted drug treatment.Methods: This study retrospectively analyzed the data of patients with advanced lung adenocarcinoma diagnosed as EGFR 19 del and L858 R sensitive mutations in the Affiliated Tumor Hospital of Guangxi Medical University from June 2016 to December 2020.Samples were collected before treatment and at the time of disease progression after the first-line EGFR-TKIs targeted therapy,and information of the types of specimens included tumor tissue,plasma and pleural effusion were also collected.Both Amplification refractory mutation system(ARMS)and next generation sequencing(NGS)were used to detect a total of 29 mutation sites of EGFR gene exon 18,19,20 and 21,observe the variation of these 29 mutation after drug resistance and analyze the their relationship with clinicopathological characteristics,efficacy and prognosis.Rank sum test was used to analyze the effects of different EGFR gene mutation states on ORR and DCR after first-line targeted therapy.The Kaplan-Meier curve was used to analyze the PFS of different EGFR gene mutation states in the retest,and the Log-Rank test was used to evaluate the survival difference.Cox proportional hazard regression model was used to evaluate the influencing factors related to PFS in different EGFR gene mutation states after retest.P<0.05 indicated that the difference was statistically significant.Results: A total of 88 patients were enrolled.Compared with the retest,the first test was mainly tissue samples,and the second test was mainly plasma samples.Before treatment,EGFR mutation rate was 100%,mainly EGFR 19 del mutation.After treatment,EGFR mutation rate was 60.4%,mainly EGFR T790 M mutation.EGFR gene mutation was detected before and after treatment,and the inconsistency rate of EGFR gene mutation was 84.09%(74/88).Among them,the inconsistent rate of EGFR gene mutation in patients with the same type of specimens was 72.22%(26/36),and the inconsistent rate of EGFR gene mutation in patients with different types of specimens was 92.31%(48/52).According to the existence or not of EGFR exon 20 T790 M and others mutation status after first-line targeted therapy,we divided the results into four groups :EGFR sensitive mutation clearance and T790 M negative group,EGFR sensitive mutation existence and T790 M positive group,EGFR sensitive mutation clearance and T790 M positive group,EGFR sensitive mutation existence and T790 M negative group.The overall ORR and DCR of all enrolled patients were69.32% and 94.31%,respectively,but there was no significant difference between the four groups.The median PFS of all patients was 10.65 months.Among them,the median PFS of EGFR sensitive mutation cleared and T790 M negative group,EGFR sensitive mutation existed and T790 M positive group,EGFR sensitive mutation cleared and T790 M positive group and EGFR sensitive mutation existed and T790 M negative group was 12.26 months,13.81 months,10.55 months and 7.96 months,respectively,and the difference in PFS between the four groups was statistically significant(P <0.05).In addition,patients with EGFR sensitive mutation clearance and T790 M negative group had longer PFS than those with EGFR sensitive mutation and T790 M negative group(12.26 months vs 7.96 months,P =0.0064).Single-factor Cox proportional hazard regression model showed that the first-line treatment efficacy evaluation of SD group and EGFR sensitive mutation existed and the T790 M positive group was the influencing factor of disease progression risk in patients with advanced lung adenocarcinoma(P <0.05).After adjusting the potential confounding factors,the multivariate Cox proportional hazard regression model showed that compared with the EGFR sensitive mutation elimination and T790 M negative group,EGFR sensitive mutation existed and T790 M positive group,EGFR sensitive mutation eliminated and T790 M positive group,EGFR sensitive mutation existed and T790 M negative group showed a gradual upward trend in the risk of disease progression,but there was no statistical significance.Among them,the risk of disease progression increased by 172 %(HR : 2.72,95 % CI : 1.33 – 5.54,P =0.0059)in the EGFR sensitive mutation group and the T790 M negative group compared with the EGFR sensitive mutation disappeared and the T790 M negative group.Conclusion: Different EGFR gene mutation types after first-line targeted therapy for advanced lung adenocarcinoma are related to PFS instead of ORR and DCR.PFS of EGFR sensitive mutation clearance and T790 M negative group was longer than that of EGFR sensitive mutation and T790 M negative group.After the progress of first-line targeted drug therapy,EGFR mutation was detected again in patients with T790 M negative advanced lung adenocarcinoma with EGFR sensitive mutation,whether EGFR mutation was eliminated was an independent influencing factor for PFS.