First-Line Immune-Combination Therapy for Driver Gene-Negative NSCLC With Brain Metastases: Real-World Outcomes.

Background: Optimal treatment for driver gene-negative non-small cell lung cancer (NSCLC) with brain metastases (BM) remains unclear, particularly regarding immune checkpoint inhibitor (ICI)-based combinations and local BM therapy. Predictive biomarkers for intracranial efficacy are also undefined.

Methods: This retrospective study analyzed driver gene-negative NSCLC patients with BM treated with first-line ICI-based systemic therapy (ICI plus chemotherapy [ICI + CT] or ICI + CT plus bevacizumab [ICI + CT + Bev]) from June 2019 to June 2024. The intracranial progression-free survival (icPFS), progression-free survival (PFS), and overall survival (OS) were compared between treatment groups and by BM local therapy. The PD-L1 tumor proportion score (TPS) expression was evaluated for correlation with intracranial efficacy.

Results: A total of 36 patients were enrolled in the study. The intracranial objective response rate (icORR) was 70.6% (ICI + CT) versus 78.6% (ICI + CT + Bev) (p = 0.689), with no significant differences in icPFS, PFS, or OS between the two different first-line systemic regimens (all p > 0.05). Local BM therapy (n = 18) did not improve icPFS and OS (all p > 0.05). Extracranial PD-L1 (TPS ≥ 50%, n = 13) correlated with superior icPFS, PFS, and OS (all p < 0.05) versus PD-L1 TPS < 50%. Multivariate analysis confirmed PD-L1 ≥ 50% as an independent prognostic factor (HR = 0.155; 95% CI, 0.025-0.939; p = 0.042).

Conclusions: Adding bevacizumab to first-line ICI-chemotherapy did not enhance survival outcomes. Local treatment for BM did not provide additional survival advantages when combined with first-line ICI-based systemic therapy. Extracranial PD-L1 TPS ≥ 50% predicted improved intracranial efficacy.