Efficacy and Safety of Radiotherapy Plus EGFR-TKIs in NSCLC Patients with Brain Metastases: A Meta-Analysis of Published Data

Background: The role of radiotherapy (RT) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains controversial. Therefore, we conducted a meta-analysis to comprehensively evaluate the efficacy and safety of RT plus EGFR-TKIs in those patients. Materials and Methods: Relevant literatures published between 2012 and 2017 were searched. Objective 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. Results: Twenty-four studies (2810 patients) were included in the analysis. Overall, RT plus EGFR-TKIs had higher ORR (RR = 1.32, 95%CI: 1.13-1.55), DCR (RR = 1.12, 95%CI: 1.04-1.22), and longer OS (HR = 0.72, 95%CI: 0.59-0.89), I-PFS (HR = 0.64, 95%CI: 0.50-0.82) than monotherapy, although with higher overall AEs (20.2% vs 11.8%, RR = 1.34, 95% CI: 1.11-1.62). Furthermore, subgroup analyses found concurrent RT plus EGFR-TKIs could prolong OS (HR = 0.69, 95%CI: 0.55-0.86) and I-PFS (HR = 0.57, 95%CI: 0.44-0.75). Asian ethnicity and lung adenocarcinoma (LAC) patients predicted a more favorable prognosis (HR = 0.69,95%CI: 0.54-0.88, HR = 0.66, 95%CI: 0.53-0.83, respectively). Conclusion: RT plus EGFR-TKIs 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 AEs of RT plus EGFR-TKIs were tolerated.