Comparison of up-front radiotherapy and TKI with TKI alone for NSCLC with brain metastases and EGFR mutation: A meta-analysis

Objective: About 50-70% non-small cell lung cancer (NSCLC) patients with EGFR mutation go through brain metastases (BM). Radiotherapy is the standard treatment before the tyrosine kinase inhibitor (TKI) era. However, the TKI has more than 70% intracranial response rate. Here, we performed a meta-analysis to compare clinical outcomes of up-front radiotherapy and TKI with TKI alone for NSCLC with BM and EGFR mutations. Methods and materials: We searched Embase, Pubmed, Web of Science, Medline, the Cochrane Library and important oncology meetings comparing the up-front radiotherapy (RT) and TKI with TKI alone in NSCLC patients with newly diagnosed BM and EGFR mutation from database inception to December 2017. We conducted meta analyses evaluating intracranial progression-free survival (iPFS) and overall survival (OS) with hazard ratios (HR) and 95% confidence intervals (CI) based on the HR of individual study. Results: Seven studies with 1086 patients were eligible for meta-analyses. Compared to TKI alone, up-front RT and TKI showed better iPFS (HR = 0.72, 95%Cl: 0.53-0.97, p = 0.028) and OS (HR = 0.70, 95%CI 0.53-0.93, p = 0.015). Meta regression analyses and subgroup analyses demonstrated patients with limited number of brain metastases benefited more from up-front RT on OS (HR: 0.54, 95% CI: 0.41-0.72, p = 0.000). Conclusion: Compared with TKI alone, up-front RT and TKI had a higher iPFS and OS, especially for patients with limited number of brain metastases. Larger randomized trials evaluating these two treatment arms are needed to identify optimal treatments for specific patients.