Introduction: Previous studies suggested that epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKIs) plus bevacizumab could significantly prolong progression-free survival (PFS) than EGFR-TKI alone as first-line setting for patients with EGFR-mutant non-small-cell lung cancer (NSCLC). However, whether this combination could benefit patients with multiple brain metastases (BrMs) remains undetermined.

Methods: A total of 208 patients with EGFR-mutant NSCLC and multiple BrM (number >3, at least one of lesions was measurable) were retrospectively identified. Kaplan-Meier curves with two-sided log-rank tests and Cox proportional hazards model with calculated hazard ratios and 95% confidence intervals were used to determine the survival difference.

Results: Of all patients, 149 patients received EGFR-TKIs monotherapy and 59 received EGFR-TKIs plus bevacizumab as first-line setting. EGFR-TKIs plus bevacizumab was associated with a significantly higher intracranial objective response rate (ORR, 66.1% vs. 41.6%, P = 0.001), systemic ORR (74.6% vs. 57.1%, P = 0.019), longer intracranial PFS (14.0 vs. 8.2 months; P < 0.001) and systemic PFS (14.4 vs. 9.0 months; P < 0.001). Importantly, addition of bevacizumab also had a significantly longer overall survival (OS, 29.6 vs. 21.7 months; P < 0.001). Multivariate analysis consistently revealed that addition of bevacizumab was independently associated with prolonged intracranial and systemic PFS, and OS. No unexpected serious adverse effects were observed.

Conclusions: EGFR-TKIs plus bevacizumab prolonged not only PFS but also OS in patients with EGFR-mutant NSCLC and multiple BrMs when compared with EGFR-TKIs alone, indicating that this combination could be an alternative therapeutic option for those patients.