Efficacy And Prognosis Of Advanced NSCLC Patients Harbored EGFR Sensitive Mutation Treated With Icotinib

Objective: To analyze the efficacy and prognostic factors of advanced NSCLC patients harbored EGFR sensitive mutation treated with Icotinib,retrospectively.To explore that the difference in efficacy and prognosis between first-line treatment and second-line and more treatment with Icotinib.Methods: The clinicopathological characteristics and survival data of NSCLC patients with histological or cytologically confirmed were collected in the Fourth Hospital of Hebei Medical University from 2012 to 2017.All patients were treated with icotinib in first-line or above.A total of 262 NSCLC patients meeting the criteria of inclusion and exclusion were included.Among whom 8 cases were excluded and 4 cases were lost(the rate of missing follow-up was 1.5%)by May 31,2018.Data analysis was performed in 250 patients with EGFR mutation-positive NSCLC.The clinical and survival data were analyzed using software SPSS 24.0.Patient OS and PFS were assessed using the Kaplan-Meier method.The log-rank test was used for comparison of survival curves of different characteristics.Prognostic factors for OS and PFS were analyzed by univariate and multivariate analysis.Statistical significance was set at P<0.05.Results:1)The efficacy and survival analysis of the total population: the objective response rate(ORR)was 62%;The median progression-free survival(mPFS)was 13 months(95% CI:11.8-14.2),1st,2nd,and 3rd-year progress-free survival rate were 53.6%,20.6%,10.0%,respectively.The median overall survival(mOS)was 27 months(95% CI:23.4-30.6),1st,2nd,and 3rd-year overall survival rates were 85.6%,56.5% and 31.8%.Univariate analysis showed that treatment line numbers,PS score,stage,number of metastatic organs,rash,brain metastasis,and optimal outcome(CR+PR)were prognostic factors for PFS(P=0.015,P=0.004,P=0.024,P<0.001,P<0.001,P=0.009,P<0.001).Multivariate regression analysis of Cox model with stepwise regression showed that rash,bone metastasis and optimal outcome(CR+PR)were independent prognostic factors for PFS(P< 0.001,P=0.05,P<0.001).Univariate analysis showed that PS score,stage,number of metastatic organs,rash,brain metastasis,bone metastasis,optimal outcome(CR+PR)and PFS were the prognostic factors for OS(P<0.001,P=0.03,P<0.001,P<0.001,P<0.001,P=0.019,P<0.001,P<0.001).Sex,number of metastatic organs,brain metastasis,optimal outcome(CR+PR)and PFS were independent prognostic factors for OS(P=0.039,P=0.015,P=0.045,P=0.02,P=0.003).2)Differences in efficacy and survival between first-line subgroup and multi-line subgroup(second and more line): among the 250 patients with EGFR mutation-positive NSCLC,there were 199 patients in the first-line subgroup and 51 patients in the multi-line subgroup.The ORR of patients in the first-line subgroup and the multi-line subgroup were 63.3% and 56.9%,respectively.There was no significant difference between both groups(P=0.397).The median PFS(14.0 months,95% CI:12.4-15.6)of patients in the first line subgroup was better than that of patients in the multi-line group(10.0 months,95% CI:7.9-12.1,P=0.015),1st,2nd and 3rd-year progression-free survival rates were 59.3%,22.3%,11.4% and 32.8%,13.9%,not reached,respectively.There was no significant difference in median OS between first-line subgroup(28 months,95% CI:23.1-32.9)and multi-line subgroup(27 months,95% CI:20.9-33.1)(P=0.888).The 1st,2nd and 3rd-year overall survival rates were 85.0%,55.9%,33.3% and 87.6%,59.4% and 30%,respectively.Univariate analysis showed that age,PS score,stage,previous surgery,number of metastatic organs,rash,and optimal outcome(CR+PR)were prognostic factors for PFS of patients in first-line subgroup(P=0.014,P=0.01,P=0.023,P=0.042,P=0.011,P<0.001,P<0.001),and the multivariate analysis of Cox model showed that optimal outcome(CR+PR),rash were the independent prognostic factor for PFS of patients in the first-line subgroup(P<0.001,P<0.001).Univariate analysis showed that PS score,pathological type,stage,previous operation,number of metastatic organs,rash,optimal outcome(CR+PR),brain metastasis,bone metastasis,PFS were prognostic factor for OS of patients in first-line subgroup(P<0.001,P=0.017,P=0.006,P=0.007,P<0.001,P<0.001,P<0.001,P=0.028,P=0.005,P<0.001,),and the multivariate analysis showed that age,PS score,previous operation,and PFS were independent prognostic factor for OS of patients in first-line subgroup(P=0.004,P<0.001,P=0.003,P<0.001).Univariate analysis showed that PS score,number of metastatic organ,rash,and brain metastasis were the prognostic factors for PFS of patients in multi-line subgroup(P=0.013,P=0.005,P <0.001,P <0.001),and the multivariate analysis showed that age and pathological type,rash were independent prognostic factor for PFS of patients in the multi-line subgroup(P=0.011,P=0.012,P <0.001);Univariate analysis showed that PS score,number of metastatic organ,rash,brain metastasis,gender,previous operation were prognostic factors for OS in multi-line subgroup patients(P=0.04,P<0.001,P=0.004,P<0.001,P=0.006,P=0.005),and the multivariate analysis showed that previous operation and rash were independent prognostic factor for OS of patients in multi-line subgroup(P=0.022,P=0.03).Conclusion:1.Icotinib was effective in the treatment of NSCLC patients harbored EGFR sensitive mutation.Rash and optimal outcome were the independent prognostic factor for PFS,while the optimal outcome and PFS were the independent prognostic factors for OS.2.The mPFS of patients with first-line Icotinib subgroup was better than that of multi-line subgroup,but there were no significant difference in ORR and OS between the two groups.It was suggested that the sooner the EGFR-TKI was used in the EGFR mutation-positive NSCLC patients,the better PFS would be obtained.It was also suggested that NSCLC patients with EGFR sensitive mutation still should be recommended to use EGFR-TKI in the subsequent therapy for the benefit of OS,even if they were not treated with EGFR-TKI in the first-line.3.Rash and initial efficacy(CR+PR)were good prognostic factor for PFS of patients in the first-line Icotinib,while PFS > 6 months was the good prognostic factors for OS of patients in the first-line Icotinib.Rash was a good prognostic factor for PFS of patients in multi-line subgroup,and it was also a good prognostic factor for OS in this group.