Efficacy and CNS Toxicity of Nivolumab and Ipilimumab in Rare Cancer Brain Metastases: A Multicenter 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 2 weeks) and ipilimumab (1 mg/kg every 6 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 objective response rate (ORR) was assessed by RECIST version 1.1, and adverse events were graded using Common Terminology Criteria for Adverse Events version 5.0. Intracranial outcomes were assessed in a subset of patients with BM to evaluate the 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 central nervous system 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. See related commentary by Ricci and Rizzo, p. 1921.