Clinical Observation Of 64 Patients With Advanced Non-small Cell Lung Cancer With EGFR Mutation Treated With Osimertinib

Objective:Molecular targeted therapy is an important means of treatment for non-small cell lung cancer(NSCLC)driven by positive genes.Among them,epithelial growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)has become the epithelial growth factor receptor,EGFR)standard treatment for advanced NSCLC patients with gene sensitive mutations,and the efficacy is superior to chemotherapy.A number of previous clinical studies have shown that third-generation EGFR-TKI Osimertinib(AZD9291)has a definite efficacy advantage in both secondary drug resistance patients with T790M mutation and first-line treatment,and it is well tolerated.The purpose of this study is to investigate the clinical efficacy and safety of third-generation EGFR-TKI in the treatment of advanced EGFR mutant NSCLC in the real world.Methods:A total of 64 inoperable locally advanced and metastatic NSCLC patients with EGFR gene mutation who were admitted to the first affiliated hospital of dalian medical university from January 1,2017 to June 30,2019 were retrospectively collected.All patients were pathologically diagnosed with NSCLC and were treated with osimertinib as a first-line,second-line or above treatment(80 mg per day orally)until the disease progressed or became intolerant of adverse reactions.Efficacy and safety were evaluated every 6 weeks.Objective response rate(ORR)and disease control rate(DCR)of osimertinib were analyzed,while long-term outcome indexes such as progression-free survival(PFS)and overall survival(OS)were analyzed.The e safety indicators include the classification and classification of adverse reactions and the reduction or withdrawal of drugs due to adverse reactions.Efficacy was evaluated according to RECIST 1.1 Criteria for efficacy evaluation of solid tumors,and Adverse drug reactions were graded according to the fourth edition of Common Terminology Criteria for Adverse Events(CTCAE).The follow-up methods included consulting the outpatient and inpatient HIS systems and telephone follow-up of patients.The follow-up deadline was December 31,2019.SPSS 22.0 software was used for statistical analysis.This study was descriptive analysis:kaplan-meier method was used for survival analysis,and log-rank test was used for univariate analysis.Results:1.General information of patients:among the 64 patients,42(65.6%)were females and 22(34.4%)were males.There were 58 non-smokers(90.6%)and 6 smokers(9.4%).The ECOG score was 0-2 points in 56 cases(87.5%)and 3-4 points in 8 cases(12,5%).There were 61 cases of adenocarcinoma(95.3%)and 3 cases of squamous cell carcinoma(4.7%).There were 1 case(1.6%)in stage IIIB and 63 cases(98.4%)in stage Ⅳ.There were 6 cases(9.4%)of first-line osimertinib,58 cases(90.6%)of second-line or above,2 cases(3.1%)of first-line treatment,1 case(1.6%)of rare mutation,3 cases(4.7%)of EGFR 19del+T790M,4 cases(6.3%)of EGFR 19del+T790M,3 cases(4.7%)of EGFR 21L858R,and 29 cases(45.3%)of EGFR 19del+T790M,EGFR 21L858R+T790M in 22 patients(34.4%).25 patients(39.1%)had received chemotherapy and 39 patients(60.9%)had not.There were 57 patients(89.1%)who had received EGFR-TKI in the first or second generation,and 7 patients(10.9%)who had not received EGFR-TKI in the first or second generation.There were 49 cases(76.6%)with the number of distant transferred organs ≤3,and 15 cases(23.4%)with>3.Brain metastases were present at baseline in 22(34.4%)patients and in 42(65.6%)patients without brain metastases.2.In terms of efficacy:the overall ORR was 43.8%,DCR was 92.2%,median progression-free survival time(mPFS)was 12.2 months(95%CI(8.4,16.0)months),and median overall survival time(mOS)was 20.6 months(95%CI(16.3,24.9)months).The difference of DCR between non-smoking patients and smoking patients was statistically significant(P=0.001),and the number of distant metastasis organs ≤3 was statistically significant(P=0.010)compared with that of patients with>3.There was no significant difference in ORR between first-line and second-line ORR treatment(P=0.449),and DCR could not be calculated.The median PFS of the first-line treatment was not achieved,and the median PFS of the second-line and above treatment was 11.8 months(95%CI(8.6,15.1)months).The median PFS of the first-line treatment was longer than that of the second-line and above treatment,and the difference was statistically significant(P=0.035,χ2=4.463).The median OS of first-line treatment was not achieved,and the median OS of second-line treatment and above was 19.6 months(95%CI(14.4,24.8)months),with no statistically significant difference(P=0.066,χ2=3.385).There was no significant difference in ORR between patients with brain metastasis and those without brain metastasis(P=1.000),and no significant difference in DCR(P=1.000).The median PFS of patients with brain metastases and without brain metastasis were 11.0 months(95%CI(8.3,13.7)months and 15.2 months(95%CI(10.3,20.1)months),there was no statistically significant difference(P=0.211,χ2=1.565),the mOS 22.3 months(95%CI(16.6,28.0)months and 20.6 months(95%CI(13.3,27.9)months),there was no statistically significant difference(P=0.735,χ2=0.114).According to the results of univariate analysis,smoking history and ECOG score were correlated with patients’ PFS and OS(P=0.000,P=0.011),and non-smoking patients with ECOG score of 1-2 had a better prognosis.3.Safety:the overall safety of the patients was better after treatment,and the main adverse reactions included rash(34.4%),diarrhea(31.3%),dry skin(28.1%),nausea(23.4%)and paronychitis(15.6%).Most of the adverse reactions were graded at grade 1 to 2,and the patients were able to tolerate the related adverse reactions,which could be significantly alleviated after symptomatic treatment and continued treatment.Conclusion:1.The efficacy of osimertinib in the treatment of EGFR gene mutation in patients with inoperable locally advanced and metastatic NSCLC was good,and the efficacy of osimertinib in patients with baseline and brain metastasis was good.Smoking history and the number of distant metastasis organs had statistical significance on patients’ DCR,and smoking history was related to the long-term efficacy of patients.Compared with smoking patients,non-smoking patients had longer PFS and OS,and ECOG score was related to patients’ PFS.Patients with an ECOG score of 0-2 had longer PFS than patients with an ECOG score of 3-4.The first-line oral osimertinib patients had better efficacy than the second-line and above patients,and there was no statistical significance in ORR and DCR between the two groups.2.The patient has few toxic and side effects and is well tolerated when taking osimertinib.It is recommended to observe whether there is any rash and diarrhea during the treatment process and promptly deal with the symptoms.For serious adverse reactions,such as interstitial pneumonia,vigilance and timely effective intervention are needed.