A Retrospective Analysis Of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) With Or Without Chemotherapy For Advanced Lung Adenocarcinoma

Background and ObjectiveLung cancer is the most frequent and lethal cancer in the world.More than half of patients have reached the advanced stage when they were diagnosed,and thus advanced patients mainly depends on drug treatment.As one of the standard treatment models,chemotherapy has reached the bottleneck with a median overall survival of 7.2-8.4 months.With the study of genomics and signal transduction,the discovery of specific molecular alterations which drive tumor growth produce a new method,targeted therapy.About half of the patients with lung adenocarcinoma have driver gene mutations,such as epidermal growth factor receptor(EGFR),which are more common in Asian,female,and non-smoker adenocarcinoma populations.Within the last decade,the application of targeted inhibitor has gradually popularized,especially for the epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs).They are superior to standard chemotherapy in first-line treatment for patients with activating EGFR mutations.The EGFR-TKIs such as gefitinib,erlotinib,ectinib and osimertinib,have been recommended as first option for advanced non-small cell lung cancer(NSCLC)with EGFR mutation by most clinical guidelines.However,acquired resistance inevitably develops with the use of drugs in practice.Given the wide variety of EGFR-TKI resistance mechanisms identified so far,seeking a combination therapy to decrease the emergence of resistance is a new strategy.Findings from several randomized controlled trials have demonstrated that the combination therapy has significantly prolonged the survival time of patients,as well as produced more side effects and affect quality of life.The strategy of EGFR-TKI combined with chemotherapy have not been widely used in the first-line treatment.This study retrospectively analyzed the differences of efficacy and safety between the EGFR-TKIs plus pemetrexed-based chemotherapy and EGFR-TKIs alone in first-line treatment of advanced adenocarcinomas,aimed to identify the population which could benefit from combination therapy.MethodsFrom December 1st,2016 to May 31st,2019,a total of 90 patients with advanced lung adenocarcinoma in EGFR-positive tumors admitted by Henan Provincial People’s Hospital were enrolled in this study.44 patients received EGFR-TKIs plus chemotherapy were named combined group,and 46 patients only received EGFR-TKIs were the monotherapy group.The basic characteristics,tumor status,pathological data,were collected,and the treatment effects and adverse reactions were observed.Objective response rate(ORR),Disease control rate(DCR),and Progression free survival(PFS)were assessed.Kaplan-Meier method was used for survival analysis,and Cox regression model was used for multivariate analysis.A two-side P value of less than 0.05 was considered statistically significant.Results1.No statistical differences in baseline data between the two groups.2.The objective response rate(ORR)of the combination group was 59.1%and 43.5%of the monotherapy group.The disease control rate(DCR)were 100%in both groups.No statistically significant difference were observed both in ORR(P=0.139)and DCR between two groups.3.The median PFS in the combination group was 12 months(95%CI:10.268～13.732),and the median PFS was 8 months(95%CI:6.096～9.904).The difference was statistically significant(P=0.013).In the subgroup analysis,patients in stage M1a,patients with EGFR21L858R-positive tumors and patients with better performance status(PS 0)had longer PFS in combination therapy than the monotherapy group(P<0.05).4.The incidence of fatigue,hair loss,adverse effects of blood system and digestive system was higher in the combination group,and the difference was statistically significant(P<0.05).Most of the treatment-related adverse events were in grades 1-2 in both groups and were tolerable.ConclusionIn the first-line treatment of advanced lung adenocarcinomas harboring EGFR-sensitive mutations,the first generation of EGFR-TKIs plus pemetrexed-based chemotherapy significantly improved the PFS of patients,especially for those with in stage M1a,patients with EGFR21L858R-positive tumors and patients with better performance status.The combination therapy increased the incidence of adverse events,but all were expected and tolerable.