Efficacy and CNS Toxicity of Nivolumab and Ipilimumab in Rare Cancer Brain Metastases: A Multi-Center Basket Trial Analysis (NCI/SWOG S1609)

PURPOSE: To evaluate the efficacy and safety of dual immune checkpoint inhibitors (ICI) in patients with brain metastases (BM) from rare cancers.

PATIENTS AND METHODS: Patients with and without BM received nivolumab (240 mg every two weeks) and ipilimumab (1 mg/kg every six weeks) (NCI/SWOG S1609 DART trial, NCT02834013) across >1,000 sites. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method; hazard ratios (HR) with 95% confidence intervals (CI) were derived from Cox models. Systemic ORR was assessed by RECIST v1.1, and adverse events were graded using CTCAE v5.0. Intracranial outcomes were assessed in a subset of patients with BM to evaluate best intracranial response.

RESULTS: Among 727 patients, the systemic ORR was 11.5% in those without BM (n=707) and 10% in those with BM (n=20) (p=0.76). PFS and OS were similar between groups (PFS: HR=1.29, 95% CI 0.81-2.07, p=0.28; OS: HR=1.36, 95% CI 0.81-2.27, p=0.24). Intracranial response was evaluable in 12 patients with BM (60%). No intracranial complete or partial responses were observed, and six patients (50%) achieved intracranial stable disease as their best intracranial response. Grade ≥3 CNS toxicities occurred in 3% of patients without BM and 5% of those with BM (p=0.43).

CONCLUSIONS: Dual-ICI therapy showed comparable efficacy and safety in patients with and without BM.