Efficacy And Safety Of Radiotherapy Plus EGFR TKI In NSCLC Patients With Brain Metastasis

Background: The role of radiotherapy(RT)combined with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)in non-small cell lung cancer(NSCLC)patients with brain metastasis(BM)remains controversial.Therefore,we conducted a meta-analysis and a retrospective analysis to comprehensively evaluate the efficacy and safety of RT plus EGFR-TKI in NSCLC patients with BM.Materials and Methods: Relevant literatures published between 2012 and 2018 were searched.Overall response rate(ORR),disease control rate(DCR),overall survival(OS),intracranial progression-free survival(I-PFS)and adverse events(AEs)were extracted.The combined hazard ratios(HRs)and relative risks(RRs)were calculated using random effects models.Meanwhile,a retrospective analysis of NSCLC patients with BMs from January 2016 to February 2019 in the First Affiliated Hospital of Nanjing Medical University was reviewed.OS、I-PFS、6-month、12-month、2-year survival rate and response rate were calculated.Outcomes were estimated by Kaplan-Meier survival analysis and log-rank test statistics.Chi-square analysis and T test were used for categorical variables and measurement data,respectively.Statistical significant differences were regarded as P<0.05.Results: Twenty-four studies(2810 patients)were included in the meta-analysis.In overall,RT plus EGFR TKI resulted in higher ORR(RR=1.32,95%CI: 1.13-1.55,P<0.001),DCR(RR=1.12,95%CI: 1.04-1.22,P=0.005),and longer OS(HR=0.72,95%CI: 0.59-0.89,p=0.002),I-PFS(HR=0.64,95%CI: 0.50-0.82,P<0.001)than monotherapy,although with higher overall incidence rate of AEs(20.2% vs 11.8%,RR=1.34,95% CI: 1.11-1.62;P=0.003).Subgroup analyses found concurrent RT plus EGFR TKI could prolong OS(HR=0.69,95%CI: 0.55-0.86,P=0.001)and I-PFS(HR=0.57,95%CI: 0.44-0.75,P<0.001).Lung adenocarcinoma(LAC)patients predicted a more favorable prognosis,with HR 0.69(95%CI: 0.54-0.88,P=0.003)and 0.58(95%CI: 0.43-0.76,P<0.001)for OS and I-PFS respectively,and better OS(HR=0.66,95%CI: 0.53-0.83,P<0.001)and I-PFS(HR=0.67,95%CI: 0.52-0.86,P=0.001)were found in Asians.Furthermore,146 NSCLC patients with BMs were included in the retrospective analysis.Overall,RT+EGFR TKI resulted in longer OS(20 month vs12 month,P=0.033)and I-PFS(12 month vs 8 month,P=0.047),with higher survival rate(6-month,84.9% vs 66.7%,P=0.017;12-month,60.4% vs 44.1%,P=0.042;2-year,35.8% vs 19.1%,P=0.028)and response rate(6 month,66.0% vs 44.1%,P=0.011;12 month,35.8% vs 19.1%,P=0.028)than RT/TKI monotherapy.However,stratification analysis found that RT+TKI versus TKI alone showed no improvement in OS(20 month vs 19 month,P=0.508),although prolong I-PFS(16 month vs 8month,P=0.041)in NSCLC patients with BM.Sequential treatment could prolong OS(28 month vs 16 month,P=0.041)without I-PFS(12 month vs 11 month,P=0.582)than concurrent RT+TKI.LAC patients with EGFR mutation and ki-67 ≤ 30% with RT+TKI treatment was a better prognosis.Conclusion: RT plus EGFR-TKI had higher response rate,longer OS and I-PFS than monotherapy in NSCLC patients with BM.Asian LAC patients with EGFR mutation had a better prognosis with concurrent treatment.The common AEs of RT plus EGFR TKI were rash,dry skin and diarrhea,the AEs were tolerated.