P08.02.B HIGH-GRADE IMMUNE-RELATED ADVERSE EVENTS AND PATIENT OUTCOMES FOLLOWING POST-OPERATIVE CHECKPOINT INHIBITION IN RESECTED BRAIN METASTASES: A RETROSPECTIVE COHORT STUDY

Abstract BACKGROUND Immune checkpoint inhibitors (ICIs) are increasingly used in patients with brain metastases, yet their postoperative safety and efficacy remain unclear. This study evaluates survival outcomes and high-grade immune-related adverse events (irAEs) in patients receiving ICIs after brain metastasis resection. MATERIAL AND METHODS We retrospectively analyzed patients who underwent brain metastasis resection followed by ICI therapy. Kaplan-Meier estimates were used to evaluate overall survival (OS), intracranial progression-free survival (icPFS), and extracranial progression-free survival (ecPFS). Only CTCAE v5.0 grade 3-4 irAEs were included. RESULTS A total of 115 patients were included (median age 64 years, 47.8% female). Most had non-small cell lung cancer (NSCLC, 71.3%) or melanoma (25.2%). The most common site was the frontal lobe. Extracranial metastases were present in 52.6%, and preoperative systemic therapy or radiation was given in 28%. Median GPA was 2.0 and postoperative KPS was 81.4. Patients received pembrolizumab (49.6%), nivolumab ± ipilimumab (35.7%), or atezolizumab (14.8%). Median ICI cycles were 4 for NSCLC and 5 for melanoma. Grade 3-4 irAEs occurred in 13 patients (11.3%), half of whom received combination therapy. The median time to irAE onset was 58 days (95% CI: 45-151). Pneumonitis (7.8%), colitis (5.2%), and hepatitis (3.5%) were most frequent. No neurologic irAEs occurred. Patients with irAEs had more melanoma, higher brain metastasis burden, extracranial disease, and higher perioperative dexamethasone exposure, although p-values were not significant after correction for multiple testing. No differences were seen in age, sex, GPA, KPS, PD-L1 status, ICI type, or cycle number. Median OS was 26.3 months in irAE-positive vs 22.0 months in irAE-negative patients (p = 0.3). icPFS was 8.4 vs 12.5 months (p = 0.4), and ecPFS was 15.2 vs 12.5 months (p = 0.6). CONCLUSION Postoperative ICI demonstrated an acceptable safety profile, with severe irAEs occurring in 11.3% of cases. No neurological irAEs were observed. Survival outcomes were comparable to existing data on brain metastases. Of note, no survival benefit was observed in patients that developed high-grade irAEs. These findings warrant further prospective studies to evaluate long-term efficacy and toxicity.