Therapy Response To EGFR-TKI In Elderly And Young Patients With NSCLC: A Systematic Review And Meta-analysis

Objective:The available clinical data were analyzed to evaluate the efficacy of EGFR tyrosine kinase inhibitors(TKIs)in elderly and younger advanced non-small cell lung cancer patients with EGFR mutations.Methods:Through the development of corresponding search strategies,Pub Med,Embase,web of science,Cochrane Library,CNKI,Wanfang database were searched for the efficacy or safety and clinical outcome studies of EGFR-TKI therapy in advanced NSCLC patients with EGFR mutations in different age ranges.The researchers screened the literature by inclusion and exclusion criteria,and extracted first authors,year of publication,title,study type,sample size of experimental group and control group,the results include progression-free survival(PFS)band their hazard ratio(HR)and 95% confidence interval(95% CI),respectively,and the quality of the literature was assessed using The Cochrane Collaboration's tool and the NewcastleOttawa scale(NOS),all the analysis using Rev Man 5.3 and Stata12.0 statistics Software.In addition,we retrospectively analyzed 40 eligible young(?45 years)non-small cell lung cancer patients admitted to the First Affiliated Hospital of China Medical University from January 1,2009 to September 1,2017,Data processing using SPSS 16.0 statistical software,analysis using Kaplan-Meier,Log-rank test and COX risk proportional model method,and the final analysis included in the young group metaanalysis.Results:A total of 678 articles were retrieved and finally screened for 7 studies,including 4 randomized controlled trials of age ?65 and 3 retrospective cohorts of ?45 years of age.Since the types of articles were different,we grouped them for evaluation.Considering that the youth group(? 45 years old)is less involved in the study,this paper retrospectively analyzed the eligible 40 cases of young NSCLC admitted to our department and included the results in a meta-analysis.The final group of elderly patients were enrolled in 268 cases,110 cases of youth group.All four studies in the elderly group were phase III clinical trials,which EGFR-TKIs were used in first-line therapy.In the youth group,except for one of the studies,the others were used in firstline therapy.In the elderly group,EGFR mutations included the deletion of exon 19 and the mutation in exon 21 of L858 R,whose controls included standard chemotherapy,paclitaxel plus carboplatin,gemcitabine plus carboplatin.In the youth study,the four study control groups were all standard chemotherapy.A retrospective analysis of 40 patients with NSCLC showed a median PFS of 12 months versus 5 months in the EGFR-TKI-treated versus chemotherapy group(HR = 0.42,95% CI 0.18-0.95 P = 0.037);Analysis of the EGFR mutation genotypes revealed a median PFS of 13 months at 95% CI(9.81-16.19)in the exon 19 deletion mutation and a median PFS of 7 months in the 21 exon L858 R mutation group with a 95% CI(5.80-8.20).A meta-analysis of the elderly group showed a significant improvement in PFS with EGFR-TKI in EGFR-mutated elderly NSCLC patients(HR = 0.28,95% CI 0.19-0.40;P <0.00001).The results of the youth group showed that EGFR-TKIs targeted therapy was also better than chemotherapy in patients with EGFR mutation in NSCLC(HR = 0.40,95% CI 0.22,0.72;P= 0.001).According to their heterogeneity,fixed effects models were used for both analyzes.No obvious publication bias was found in the analysis.In addition,subgroup analyzes of two common types of EGFR mutations in four randomized controlled trials were performed.Compared with chemotherapy,the results showed that treatment with EGFR TKIs demonstrated greater benefit in 19 exon deletion mutation group(HR = 0.24;95% CI 0.15,0.39;P<0.00001)than in 21 exon L858 R point mutations(HR 0.44,95% CI 0.26,0.74;P =0.002).Analysis using random effects model.Conclusion:Targeted therapy of EGFR-TKIs are superior to chemotherapy in NSCLC patients with EGFR mutation,both young and elderly.They are especially effective in delaying disease progression in elderly patients with advanced NSCLC.EGFR-TKI is an effective treatment option for this age group.The degree of benefit of young NSCLC patients lower than the elderly when receiving EGFR-TKI therapy.Patients with EGFR19 exon deletion mutations had greater benefit from EGFR-TKI treatment than did exon 21 L858 R point mutations.