Efficacy And Safety Of EGFR-TKI Combined With Early Brain Radiotherapy And TKI Alone For Nsclc With Brain Metastases And EGFR Mutation:a Meta-analysis

Objective:The incidence of brain metastases in patients with EGFR-mutated non-small cell lung cancer is high,and brain radiotherapy has been the standard of care for brain metastases,and EGFR-TKI is now recommended as the first line treatment of choice for these patients according to national and international guidelines.At present,the efficacy and safety of early intervention of brain radiotherapy are still controversial on the basis of EGFR-TKI treatment regimen.In this paper,a meta-analysis was conducted to evaluate the efficacy and safety of early brain radiotherapy combined with EGFR-TKI versus EGFR-TKI alone in patients with EGFR mutated non-small cell lung cancer brain metastases,in order to provide the best treatment option for these patients.Methods:We searched the literature published in Pubmed,Embase,Web of Science,Cochrance library,Scopus,OVID,CNKI,Wanfang,Weipu,China Biomedical Literature Database(CBM)and other databases on the efficacy and safety of early brain radiotherapy + EGFR-TKIs combination therapy and EGFR-TKI monotherapy in patients with EGFR-mutant non-small cell lung cancer with brain metastases.The search time frame was from database creation to December 31,2022.The NewcastleOttawa scale(NOS Scale)was used for literature quality assessment,with the primary outcomes being overall survival(OS)and intracranial progression-free survival(iPFS)between groups,measured by hazard ratios(HR),secondary outcomes being adverse events(AEs),measured as risk ratios(RR),with 95% CI as the confidence zone,using Rev Man 5.3 software and STATA 14.0 to perform metaanalysis of the data.Results:Eighteen retrospective studies with a total of 2119 associated patients were included.Among them,16 reported OS,14 reported iPFS,and 2 reported adverse effects.The results of the meta-analysis are as follows:1 、 Compared with EGFR-TKI alone,the combination of early brain radiotherapy + EGFR-TKI had significant benefits in OS(HR: 0.87,95% CI: 0.76-0.99,p=0.04)and iPFS(HR: 0.7,95% CI: 0.57-0.86,p=0.0005),and the results were statistically significant.2 、 In terms of adverse effects,early brain radiotherapy + EGFR-TKI combination therapy was more likely to lead to neurological adverse reactions(RR:18.63,95% CI: 2.81-123.73,p=0.002),while in terms of fatigue,rash,and diarrhea,the analysis results showed no significant significance between the two groups(p>0.05).3、 The results of subgroup analysis showed that osimertinib alone tended to benefit in OS(HR: 1.44,95% CI: 0.94-2.22,p=0.1)and iPFS(HR: 1.10,95% CI:0.76-1.6,p=0.61)in the osimertinib treatment group,but p>0.05,which was not statistically significant.In patients using first-and second-generation TKIs,the combination therapy resulted in longer OS(HR: 0.83,95% CI: 0.72-0.95,p=0.007)and iPFS(HR: 0.65,95% CI: 0.53-0.80,p<0.0001),with statistically meaningful results.Conclusion:Compared with EGFR-TKI monotherapy,early brain radiotherapy + EGFRTKIs combination therapy can obtain longer OS and iPFS,reduce the risk of death in these patients,and patients in the combination therapy group are more likely to have neurological adverse reactions,and the results are not statistically significant in terms of fatigue,rash and diarrhea.Patients treated with osimertinib alone tended to have longer OS and iPFS,but the results were not statistically significant.