EGFR Mutations In Patients With Advanced NSCLC Complicated With COPD And The Response And Prognosis Of EGFR-TKIs Treatment

Objective:1.To investigate EGFR mutation in patients with advanced NSCLC complicated with COPD;2.To analyze the curative effect and prognosis of EGFR-TKIs in patients with advanced NSCLC complicated with COPD.Methods:1.351 Patients with advanced NSCLC diagnosed by histopathology from January 1,2016 to June 30,2019 with EGFR gene detection were collected in the Department of Respiratory Medicine,Northern Jiangsu Peoples Hospital.According to whether or not with COPD,351 patients were divided into ? non-COPD advanced NSCLC group,207cases;? advanced NSCLC complicated with COPD group,144 cases.2.135 patients with advanced NSCLC were treated from first-line of first-generation EGFR-TKIs.According to whether or not with COPD and its severity,? non-COPD advance NSCLC group,95 cases;? advance NSCLC complicated with COPD of AB groups,20 cases;? advance NSCLC complicated with COPD of CD groups,20 cases.EGFR gene was detected by direct sequencing technique,ARMS and NGS.Using SPSS 19.0 statistical software to analyze the clinicopathological features of the two groups,the relationship between the incidence of the EGFR mutation and clinicopathological features,the predictive factors of EGFR mutation,the difference of EGFR mutation types between the two groups,The relationship between the severity of COPD and the curative effect and prognosis,the survival curve was drawn by Kaplan-Meier,the prognostic factors in patients with advanced NSCLC.Results:1.In advanced NSCLC complicated with COPD group,the proportion of male,older age,smoking history and ECOGPS score of 2 was higher than that of non-COPD advanced NSCLC group(P<0.05),while the proportion of adenocarcinoma,stage ?,positive EGFR mutation and EGFR-TKIs treatment was lower than that of non-COPD advanced NSCLC group(P <0.05).2.In patients with advanced NSCLC complicated with COPD,the incidence of EGFR mutation was 43.2% in women,the incidence of EGFR mutation was 40.4% in patients without smoking history;In patients with non-COPD advanced NSCLC,and the incidence of EGFR mutation was60.4% in women,the incidence of EGFR mutation was 62.2% in patients without smoking history.3.Multivariate logistic regression analysis showed that,COPD(OR=0.57,95%CI:0.34-0.96,P=0.03),smoking(OR=0.36,95%CI:0.20-0.64,P < 0.01)and squamous cell carcinoma(OR=0.39,95%CI:0.16-0.96,P=0.04)were independent risk factors for the decrease of EGFR mutation.4.There were 143 cases of EGFR positive mutation,and the overall mutation incidence was 40.7%.Among the patients with single gene mutation in EGFR,G719 X 1 case,accounted for 0.7%,19?Del 79 cases,accounted for 55.2%,T790 M 1 case accounted for 0.7%,20?ins 2 cases,accounted for 1.4%,L858 R 45 cases,accounted for 31.5%,S768 I and L861 Q were not detected.Among the patients with double gene mutations in EGFR,G719X+L861Q1 accounted for 0.7%,19?Del + L858 R 3 cases,accounting for 2.1%,L858R+L861Q 7 cases,accounting for 4.9%,19?Del + T790 M 2cases,accounting for 1.4%,and L858R+T790M 2 cases,accounting for 1.4%.Among all the mutation types,the susceptible mutation 19 EGFR and L858 R was the main mutation,accounting for 86.7% of the total mutation,which was significantly higher than that of other mutation types.Compared with the non-COPD advanced NSCLC group,there was no significant differencein EGFR gene single mutation and EGFR gene double mutation between the advanced NSCLC complicated with COPD group(P=0.56).There was no significant difference between the two groups in 19?Del,L858 R and other EGFR mutation types(P=0.36).5.Compared with the non-COPD advanced NSCLC group,the ORR and DCR of EGFR-TKIs treatment the advanced NSCLC complicated with COPD of CD groups were significantly lower(35.0% vs 64.2%,P=0.02;80.0% vs 94.7%,P=0.04).There was no significant difference in the ORR and DCR of EGFR-TKIs treatment between the advanced NSCLC complicated with COPD of CD groups and the non-COPD advanced NSCLC group(P > 0.05).6.The m PFS of non-COPD advanced NSCLC group was 11.0 months(95%CI:10.2-11.8);that of the advanced NSCLC complicated with COPD of AB groups was 10.0 months(95%CI : 9.0-11.0),and that of the advanced NSCLC complicated with COPD of CD groups was 9.0 months(95%CI :8.6-9.4).There were significant differences in m PFS between non-COPD advanced NSCLC group and the advanced NSCLC complicated with COPD of CD groups(P<0.01),there was no significant difference in m PFS between non-COPD advanced NSCLC group and the advanced NSCLC complicated with COPD of AB groups(P=0.75).7.The m OS of non-COPD advanced NSCLC group was 32.0 months(95%CI:29.0-35.0);that of the advanced NSCLC complicated with COPD of AB groups was 28.0 months(95%CI : 21.4-34.6),and that of the advanced NSCLC complicated with COPD of CD groups was 20 months(95%CI :13.3-26.7).There were significant differences in m OS between non-COPD advanced NSCLC group and the advanced NSCLC complicated with COPD of CD groups(P < 0.01),there was no significant difference in m OS between non-COPD advanced NSCLC group and the advanced NSCLC complicated with COPD of AB groups(P=0.55).8.Univariate Cox regression analysis showed that the influencing factors of PFS in patients with advanced NSCLC treated with EGFR-TKIs was COPD of CD groups(HR: 2.84,95%CI: 1.58-5.09,P<0.01).Multivariate Cox regression analysis showed that the COPD of CD groups was independent influencing risk factors of PFS in patients with advanced NSCLC treated with EGFR-TKIs(HR: 2.59,95%CI:1.43-4.69,P<0.01).9.Univariate Cox regression analysis showed that the influencing factors of OS in patients with advanced NSCLC treated with EGFR-TKIs were COPD of CD groups(HR: 2.81,95%CI: 1.37-5.76,P < 0.01),squamous cell carcinoma(HR: 4.48,95%CI: 1.56-12.89,P < 0.01).Multivariate Cox regression analysis showed that COPD of CD groups,squamous cell carcinoma were independent influencing risk factors of OS in patients with advanced NSCLC treated with EGFR-TKIs(HR:3.67,95%CI: 1.77-7.64,P < 0.01;HR:5.64,95%CI: 1.91-16.69,P<0.01).Conclusions:1.The incidence of EGFR mutation decreased in patients with advanced NSCLC complicated with COPD,and COPD was an independent risk factor for the decrease of the incidence of EGFR mutation.2.The type of EGFR mutation in patients with advanced NSCLC had no significant relationship with COPD.3.The curative effect and prognosis of patients with advanced NSCLC complicated with COPD of CD groups treated with first-generation EGFR-TKIs first-line treatment were poorer,and the COPD of CD groups was an independent risk factor affecting the prognosis of patients with advanced NSCLC.