Optimizing Lung-molGPA-Directed Therapy for EGFR/ALK/ROS1-Wildtype Non-Small Cell Lung Cancer Brain Metastases:...

Patients with non-small cell lung cancer (NSCLC) and brain metastases whose tumors lack EGFR, ALK, or ROS1 alterations have heterogeneous outcomes and limited evidence to guide treatment intensity. We assessed whether Lung-molGPA could stratify prognosis and inform treatment selection in this population. This retrospective two-center cohort included 811 patients with EGFR/ALK/ROS1-wild-type NSCLC treated between September 2013 and August 2022. Overall survival (OS) was evaluated using Kaplan-Meier methods and center-stratified multivariable Cox regression across three Lung-molGPA strata and treatment modalities. Median OS was 6.9 months (95% confidence interval [CI], 6.4-7.4) overall and 4.81 (4.20-5.30), 7.65 (6.73-8.40), and 16.00 (13.40-22.90) months in the Lung-molGPA 0-1.0, 1.5-2.0, and 2.5-3.0 groups, respectively (p < 0.001). Compared with the 0-1.0 group, adjusted mortality was lower in the 1.5-2.0 (hazard ratio [HR], 0.68; 95% CI, 0.58-0.80) and 2.5-3.0 groups (HR, 0.39; 95% CI, 0.30-0.50). Chemotherapy, immunotherapy, antiangiogenic therapy, and brain- and chest-directed local therapy were independently associated with lower mortality, although their associations varied across prognostic strata and treatment contexts. Lung-molGPA provides clinically meaningful prognostic separation and may help tailor treatment intensity for EGFR/ALK/ROS1-wild-type NSCLC with brain metastases.