Comparative safety and survival outcomes of immune checkpoint inhibitors in brain metastases from lung cancer: a propensity-matched cohort study.

purposeBrain metastases from lung cancer are associated with high morbidity and mortality. Immune checkpoint inhibitors (ICIs), including PD-1/PD-L1 and CTLA-4 inhibitors, are increasingly used, but their safety profile in this population remains poorly defined. We aim at exploring their safety and outcomes in this population.

methodsWe used TriNetX to identify patients with diagnoses of lung cancer and secondary brain metastases treated at the Mount Sinai Health System. Three cohorts were formed: PD-1/PD-L1 inhibitors (n = 330), CTLA-4 inhibitors (n = 30), and no immunotherapy (n = 800). Propensity score matching was applied to create balanced subgroups for each comparison. Outcomes assessed included hematologic toxicity, respiratory and neurologic complications, and survival, with a 3-year follow-up window. Risk ratios and Kaplan-Meier survival analysis were performed.

resultsPD-1/PD-L1 inhibitors were associated with a significantly higher incidence of anemia (40.0% vs. 13.3%; RR 3.0, OR 4.3, p < 0.001) and shorter anemia-free survival (HR 3.44, 95% CI 2.36-5.02, p < 0.001). CTLA-4 inhibitors were associated with a higher risk of seizures (33.3% vs. 10%; RR 3.33, OR 4.67, p = 0.04), anemia (66.7% vs. 33.3%, p = 0.01), and respiratory complications including intubation (26.7% vs. 10%, p = 0.04) and respiratory failure (36.7% vs. 13.3%, p = 0.01). Kaplan-Meier analysis showed a survival probability of 46.7% vs. 82.6% at 3 years for CTLA-4 (p < 0.01).

conclusionCheckpoint inhibitors are associated with increased hematologic, neurologic, and respiratory complications in patients with brain metastases from lung cancer. CTLA-4 blockade appears to carry higher toxicity than PD-1/PD-L1 inhibitors. These findings show the need for careful patient selection and close monitoring when initiating ICIs in this population.