Abstract
While ipilimumab and nivolumab has demonstrated promising intracranial activity among patients with melanoma brain metastases (BM), patients with prior systemic therapy exposure may be at higher risk of poor intracranial disease control and benefit from upfront local therapy. We evaluated outcomes of patients with BMs treated with ipilimumab/nivolumab and stereotactic radiosurgery (SRS). Overall survival (OS) and intracranial progression-free survival (PFS) were estimated from SRS using a non-parametric method, and Cox proportional hazards models were used to test clinically relevant factors. A total of 68 consecutive patients with 413 treated BMs between 2015 and 2025 were included with median follow-up of 19.3 months from SRS. At the time of analysis, 34 (53%) patients were alive. The 2-year OS and intracranial PFS for the entire cohort was 49.5% and 36.1%, respectively. 34 patients (50%) had prior exposure to immune checkpoint inhibition (ICI) and 13 patients (19%) had exposure to prior BRAF/MEK inhibition. On univariable analysis, factors significantly associated with worse OS included receipt of prior ICI (HR 2.3, 95% CI 1.24 - 4.26, p = 0.008) and BRAF/MEK inhibition (HR 2.37, CI 1.21-4.67, p = 0.012). Upfront brain metastasis resection was associated with improved OS (HR 0.39, 95% CI 0.21 – 0.73, p = 0.003). Patients with prior ICI exposure trended towards worse intracranial PFS (median intracranial PFS 5.9 months vs 15.1 months, p = 0.12) and had worse survival after SRS (median OS 17.6 months vs 50.5 months, p = 0.007). While ipilimumab/nivolumab demonstrates encouraging intracranial control and survival among patients with melanoma brain metastases, patients with prior ICI or targeted therapy exposure are at higher risk of poor outcomes and may benefit from additional treatment strategies.