Clinical Efficacy And Influence Factors Of Icotinib Combined With Chemotherapy In The Treatment Of Advanced Lung Adenocarcinoma With EGFR Sensitive Mutations

Background and purposeLung cancer is the malignant tumor with the highest morbidity and mortality in the world,which seriously threatens the life of human.According to the histopathological characteristics,lung cancer is divided into two types:non-small cell lung cancer(NSCLC)and small cell lung cancer(SCLC).NSCLC includes squamous cell carcinoma,adenocarcinoma,large cell carcinoma and so on,which accounting for more than 80%of the total number of lung cancer.Lung adenocarcinoma is the most common pathological type,accounting for about 40%of lung cancer.At present,chemotherapy of pemetrexed plus platinum drugs is the common first-line treatment options used for advanced lung adenocarcinoma.However,the 5-year survival rate of chemotherapy is not ideal,and most patients often face with the problems of recurrence,resistance,side effects during or after chemotherapy.In recent years,targeted therapies represented by epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)has made a series breakthrough for the lung adenocarcinoma patients with EGFR mutations.Besides,this kind of drugs also possess the advantages of convenient taking and fewer side effects.However,clinical studies have found that most patients had drug resistance after EGFR-TKI treatment for a period of time,resulting in the further progression of their disease.In order to delay the time of drug resistance and improve the efficacy of EGFR-TKI treatment,EGFR-TKI combined with chemotherapy as an alternative scheme has received increasing attention.Icotinib is a currently common used EGFR-TKI targeted drug for the treatment of advanced lung adenocarcinoma,but there are few studies on the clinical efficacy and influencing factors of Icotinib combined with chemotherapy for advanced lung adenocarcinoma patients.This subject retrospectively studied the clinical data of Icotinib combined with chemotherapy in the treatment of advanced lung adenocarcinoma patients with EGFR sensitive mutations,and discussed the clinical efficacy,safety and factors affecting the prognosis of patients,in order to provide clinical reference of the combination treatment for advanced lung adenocarcinoma patients with EGFR sensitive mutations.Materials and methods1 General informationThis study collected 97 advanced lung adenocarcinoma patients from the first affiliated hospital of Zhengzhou University from February 2015 to February 2018.All patients met the selection criteria and had complete data.The general clinical data has been collected and organized including age,gender,smoking history,ECOG score,clinical stage,type of EGFR mutation,etc.2 MethodsThe patients were divided into two groups according to the different treatment schemes.The control group was the Icotinib group,which treated with hydrochloride Icotinib tablets(Conmana),3 times/day,125mg/time.The observation group was Icotinib combined with chemotherapy group,which treated with pemetrexed plus platinum chemotherapy based on the medication of the Icotinib group.The chemotherapy plan was to receive 500mg/m2 intravenous infusion of pemetrexed on the first day of each treatment cycle.Carboplatin was administered intravenously at the therapeutic dose of AUC=5 on day2.3 Assessment of clinical efficacy,influence factors and safetyTwo groups were boss evaluated the short-term efficacy according to the overall response rate(ORR)and disease control rate(DCR)after 12 weeks’ treatment.RECIST assessment:disease progression(PD),disease stability(SD),partial response(PR),complete response(CR).ORR=(CR+PR)/total number of cases ×100%,DCR=(CR+PR+SD)/total number of cases × 100%.Long-term efficacy was evaluated by progression-free survival(PFS)and overall survival’(OS).The factors affecting patients’ PFS and OS were also analyzed.Besides,adverse events(AE)were classified into 5 grades according to the CTCAE5.0.4 Statistical analysisData analysis was performed by SPSS26.0 statistical software.Measurement data was expressed as X±SD and analyzed with t test.Count data was expressed as rate(%)and compared with χ2 test.Survival curve was drawn by Kaplan-Meier method,and survival analysis was performed by COX regression.The differences between two survival curves were compared with Log-rank method.Take α=0.05 as the inspection level.Results1.Comparision of general data:there was no significant difference in age,gender,smoking history,ECOG score,clinical stage,type of EGFR mutation and so on between the observation group and the control group(P>0.05).2.Comparision of short-term efficacy:the ORR was 58.14%(25/43)and 35.19%(19/54)respectively in the observation group and the control group,and the difference between two groups was statistically significant(P<0.05).The DCR was 93.02%(40/43)and 88.89%(48/54)respectively in the observation group and the control group,but there was no significant difference between two groups(P>0.05).3.Comparision of long-term efficacy:the median PFS was 19(95%CI:16.247～21.753)months and 10(95%CI:7.601～12.399)months respectively in the observation group and the control group,and the difference between two groups was statistically significant(P<0.05).The median OS was 48(95%CI:35.490 to 60.510)months and 31(95%CI:22.820 to 39.180)months respectively in the observation group and the control group,and the difference between two groups also was statistically significant(P<0.05).4.Influence factors of survival:treatment method,ECOG score,clinical stage and type of EGFR mutation were the influence factors of patients’ disease progression status(P<0.05),of which treatment method,clinical stage and EGFR mutation type were the independent factors(P<0.05).Treatment methods,age,ECOG score and clinical stage were the influence factors of patients’ overall survival status(P<0.05),of which treatment method,ECOG score and clinical stage were the independent factors(P<0.05).5.Comparision of adverse events:the incidence of total AE in the observation group and the control group were 83.72%and 35.1%respectively,and the difference between them was statistically significant(P<0.05).The observation group was significantly higher than the control group in terms of bone marrow suppression and gastrointestinal reactions(55.81%vs.3.7%;48.84%vs.12.96%,P<0.05),The incidence of high-grade AE in the observation group and the control group were 18.60%and 5.56%respectively,but there was no significant difference between them((P>0.05).Conclusions1.The ORR of lung adenocarcinoma patients with EGFR sensitive mutation in Icotinib combined with chemotherapy group is higher than that in the Icotinib group while the median PFS and OS are also longer compared with the control group,indicating that the clinical efficacy of the combined therapy is better than the monotherapy,but there are no significant differences between the two groups in high-level adverse reactions.2.Treatment method,clinical stage and EGFR mutation type are independent factors for disease progression status of patients.Treatment method,ECOG score and clinical stage are independent factors for overall survival status of patients.3.Icotinib combined with chemotherapy can be a first-line treatment option for.advanced lung adenocarcinoma patients with EGFR mutation.