COX Analysis For Survival Of Advanced Non-small Cell Lung Cancer Patients Treated With First-line Icotinib

Objective: Epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)has become an indispensable therapeutic agent for non-small cell lung cancer(NSCLC).This study retrospectively analyzed the efficacy and survival data of advanced NSCLC patients with first-line treatment of Icotinib,and explored the prognostic factors of patients with advanced NSCLC and EGFR-sensitive mutant lung adenocarcinoma.Methods: The clinicopathological data of advanced NSCLC patients treated with first-line Icotinib in the Fourth Hospital of Hebei Medical University from July 2011 to December 2017 were retrospectively analyzed.The survival data of patients were followed up,and the objective response rate(ORR),disease control rates(DCR),progression-free survival(PFS)and overall survival(OS)were calculated,and the prognostic factors for survival in advanced NSCLC and EGFR-sensitive mutant lung adenocarcinoma patients were analyzed.The statistical analysis was conducted using SPSS 21.0.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 PFS and OS were analyzed by univariate and multivariate analysis.The prognostic factors were analyzed by COX proportional hazard model.Statistical significance was set at P<0.05.Results:A total of 252 NSCLC patients were enrolled in this study,including 238 cases of adenocarcinoma(94.4%).There were 220 cases(87.3%)with EGFR gene detection,111 cases(44.1%)with EGFR 19-Del mutation and 85 cases(33.7%)with EGFR 21-L858 R mutation.The efficacy analysis of 252 patients with advanced NSCLC showed that the ORR was 57.5%(145/252),and the DCR was 86.5%(218/252).The median PFS was 13.0 months(95%CI: 11.6-14.4),and the median OS was 26.0 months(95% CI: 22.5-29.5).COX hazard model analysis showed liver metastasis(P=0.001),adrenal metastasis(P=0.039),and EGFR mutation status(P<0.001)were independent prognostic factors for PFS of NSCLC patients.Age(P=0.011),pathological type(P=0.041),previous surgical treatment(P=0.008),bone metastasis(P=0.025),number of organs with distant metastasis(P<0.001),optimal efficacy(P<0.001),subsequent targeted therapy(P<0.001),EGFR mutation status(P=0.005)were independent prognostic factors for OS of NSCLC patients.Efficacy analysis of 189 lung adenocarcinoma patients with EGFR-sensitive mutations(mainly including 19-Del and 21-L858 R mutations)showed that the ORR was 64.6%(122/189),and the DCR was 94.7%(179/189).The median PFS was 14.0 months(95% CI: 11.9-16.1),and the median OS was 28.0 months(95% CI: 22.2-33.8).COX regression model analysis showed that previous surgical treatment(P=0.014)and liver metastasis(P=0.024)were independent prognostic factors for PFS of patients with EGFR-sensitive mutation.Age(P<0.001),previous surgical treatment(P=0.006),liver metastasis(P=0.030),number of distant metastatic organs(P=0.001),optimal efficacy(P<0.001),subsequent targeted therapy(P<0.001),EGFR mutation type(P=0.005)were independent prognostic factors for OS of patients with EGFR-sensitive mutation.The ORR of the EGFR 19-Del mutant group(106 cases)and 21-L858 R mutant group(83 cases)were 67.0% and 61.5%,respectively(P=0.430),and the DCR were 96.2% and 92.8%,respectively(P=0.292).There was no significant difference for median PFS between the two groups(16.0 months,95% CI: 11.4-20.6 vs.13.0 months,95% CI: 11.7-14.3,P=0.254).However,the median OS of patients with EGFR 19-Del mutation(35.0 months,95% CI:26.7-43.3)was significantly better than that of patients with 21-L858 R mutation(25.0 months,95% CI :17.2-32.8,P=0.012).COX regression model analysis showed that previous surgical treatment(P=0.012)was an independent prognostic factor for PFS of patients with 19-Del mutation.Age(P=0.007),previous surgery(P=0.003),and number of distant metastases organ(P=0.002)were independent prognostic factors for OS of patients with 19-Del mutation.Gender(P=0.053)and initial desease staging(P=0.018)were independent prognostic factors for PFS of patients with 21-L858 R mutation.Age(P=0.017),bone metastasis(P<0.001),pleural metastasis(P=0.008),and optimal efficacy(P<0.001)were independent prognostic factors for OS of patients with 21-L858 R mutation.Conclusion:1.Icotinib is effective for patients with advanced NSCLC in first-line treatment,especially for those patients with EGFR-sensitive mutations.Liver metastasis,adrenal metastasis and EGFR mutation status were independent prognostic factors for PFS of NSCLC patients.Age,pathological type,previous surgical treatment,bone metastases,number of distant metastatic organs,optimal efficacy,subsequent targeted therapy,and EGFR mutation status were independent prognostic factors for OS NSCLC patients.2.Previous surgical treatment and liver metastasis were independent prognostic factors for PFS of patients with EGFR-sensitive mutation,while age,number of distant metastatic organs,optimal efficacy,subsequent targeted therapy,and EGFR mutant subtype were independent prognostic factors for OS of those patients.3.The median OS of patients with EGFR 19-Del mutation was significantly better than that of patients with 21-L858 R mutation,however,there were no significant differences in ORR,DCR and median PFS between both groups.There were some differences in prognostic factors between the EGFR 19-Del mutant and 21-L858 R mutant patients,which was helpful to develop clinical treatment strategies of EGFR-TKI.