Efficacy and Safety of EGFR-TKI Combined With Early Brain Radiotherapy Versus TKI Alone in Patients With EGFR-Mutated NSCLC With Brain Metastases: A Systematic Review and Meta-Analysis.

Abstract

To evaluate the efficacy and safety of early brain radiotherapy combined with EGFR-TKI versus EGFR-TKI alone in EGFR-mutation-positive non-small cell lung cancer (NSCLC) patients with brain metastases (BMS). A systematic literature search was conducted in several databases. The primary outcome measures were overall survival (OS) and intracranial progression-free survival (iPFS), while secondary outcome measures included adverse events (AEs). Meta-analysis was performed using STATA 15.1 software. A total of 18 retrospective trials involving 2,119 patients were included. Meta-analysis showed that early brain radiotherapy combined with EGFR-TKI was superior to monotherapy in improving OS (HR = 0.87, 95% CI, 0.76-0.99) and iPFS (HR = 0.77, 95% CI, 0.61-0.97). Subgroup analysis indicated that among patients treated with Osimertinib, monotherapy showed a trend towards improved OS (HR = 1.44, 95% CI, 0.94-2.22) and iPFS (HR = 1.10, 95% CI, 0.76-1.60), though without statistical significance. In contrast, first- and second-generation EGFR-TKI combined with early brain radiotherapy significantly prolonged OS (HR = 0.83, 95% CI, 0.72-0.95) and iPFS (HR = 0.72, 95% CI, 0.55-0.93). Regarding AEs, the incidence of neurological adverse reactions was significantly higher in the combined treatment group (RR = 15.82, 95% CI, 2.31-108.54). Early brain radiotherapy combined with EGFR-TKI can significantly improve OS and iPFS in EGFR-mutated NSCLC patients with BMS but may increase the risk of neurological adverse reactions. Further research is needed to verify the efficacy differences between monotherapy and combination therapy for patients using Osimertinib.