Sequential Treatment Of EGFR Tyrosine Kinase Inhibitors And Platinum Doublet Chemotherapy On Survival Of Advanced Non-small-cell Lung Cancer With EGFR Mutations

[Background]In China,70%lung cancer patients are found at late stage when they are diagnosed.The downstream signaling pathways that promote cell growth and survival are unusually dependent on epidermal growth factor receptor(EGFR).Mutations in the EGFR gene are present in 25%of non-small cell lung cancer(NSCLC)patients.Patients with advanced EGFR-mutant NSCLC may experience dramatic tumor shrinkage and durable responses with the reversible EGFR tyrosine kinase inhibitors(TKIs).Patients with advanced NSCLC can receive first-line TKI or chemotherapy followed by second-line chemotherapy or TKI as an alternative treatment.Despite the better progress-free survival(PFS)in first-line TKI therapy,the overall survival(OS)was still not significant in many prospective trials.Although the first-line TKI/second-line chemotherapy strategy is often applied in treatment,comparing with first-line chemotherapy/second-line TKI,objective response rate and total PFS of first-and second-line treatment is still unclear.Therefore,it is necessary to design a research to explore the influence of first-line chemotherapy/second-line TKI and first-line TKI/second-line chemotherapy strategies on the total PFS and objective response rate of advanced EGFR-mutant NSCLC patients.[Objectives]According to the analysis of clinical features,treatment strategy,response rate,first-line and second-line PFS of advanced NSCLC patients,we evaluated response rate and total PFS of first-line chemotherapy/second-line TKI and first-line TKI/second-line chemotherapy.Additionally,we made a meta-analysis to explore the pooled HR of overall survival of advanced NSCLC patients who received first-line chemotherapy/second-line TKI and first-line TKI/second-line chemotherapy.[Materials and Methods]We retrospectively reviewed an institutional database from January 2012 through April 2016 to identify 89 patients with sensitizing EGFR mutations who received TKI or platinum doublet chemotherapy.We analyzed the clinical features,treatment strategy,response rate,first-line and second-line PFS of patients.We made data analysis using Fisher's exact test,Wilcoxon rank sum test,logistic regression analysis,Kaplan-Meier method and multivariable Cox analysis,and P<0.05 was considered significant.We reviewed and included four randomized controlled clinical trials in meta-analysis,and recorded the author,time,patient number,treatment and hazard rate from these trials.We made a meta-analysis using Stata software to explore the pooled HR of overall survival of advanced NSCLC patients,and P<0.05 was considered significant.[Results]Eighty-nine patients were included,50 of whom were treated with first-line chemotherapy/second-line TKI and 39 of whom were treated with first-line TKI/second-line chemotherapy.We assessed the differences in the total PFS between the two strategies.The median total PFS was 14.28 months on first chemotherapy/second TKI and 17.77 months on first TKI/second chemotherapy(adjusted HR=0.96;95%confidence interval:0.56-1.66;p=0.886).A significant difference was found between two strategies on first-and second-line PFS(all P<0.001).The objective response rate was evaluable in all patients and was 52.0%for those treated with first-line chemotherapy/second-line TKI and 38.5%for those treated with first-line TKI/second-line chemotherapy.After adjusting for related factors,the odds ratio for the response rate was 2.77(95%CI:0.77-9.90;p=0.117).Additionally,there was a suggestion of benefit for first-line chemotherapy/second-line TKI compared with first-line TKI/second-line chemotherapy in the patients who were more than 54 years old,did not have brain metastasis,had L858R or other mutations,and received palliative radiotherapy.Meta-analysis of four randomized controlled clinical trials revealed that the pooled HR of overall survival of advanced NSCLC patients who received first-line chemotherapy/second-line TKI and first-line TKI/second-line chemotherapy was 0.97(95%CI:0.76-1.18;p=0.340).[Conclusions]There was no difference in the total PFS of first-line chemotherapy/second-line TKI and first-line TKI/second-line chemotherapy strategies in non-small-cell lung cancer patients.Patients who were more than 54 years old,did not have brain metastasis,had L858R or other mutations,and received palliative radiotherapy may benefit from the first-line chemotherapy/second-line TKI strategy.The difference in overall survival of patients was still not significant in our meta-analysis.