Abstract Outcomes of patients with brain metastases (BM) treated with immune checkpoint inhibitors have been previously studied, showing similar intra- and extra-cranial response rates and overall survival (OS), particularly in melanoma and lung cancer. However, data on rare tumors with BM remain limited. We report efficacy and toxicity outcomes from the largest basket trial for rare cancers. Rare tumor patients were treated with nivolumab (NIVO, 240 mg Q2W) and ipilimumab (IPI, 1 mg/kg Q6W) in the federally funded SWOG S1609 DART trial (NCT02834013), conducted at over 1,000 sites. The protocol was approved by SWOG, the NCI, and institutional review boards. Outcomes were compared between patients with and without BM at enrollment. Progression-free survival (PFS) and OS were estimated using Kaplan-Meier methodology. Tumor response was assessed per RECIST v1.1; toxicities were graded per CTCAE v5.0. Hazard ratios (HR) with 95% confidence intervals (CI) and P-values were calculated. Among 727 patients, response rates were 11% in patients without BM (n=707) and 10% in those with BM (n=20). PFS and OS were similar between patients with and without BM (HR for PFS=1.29 0.81–2.07, P=0.28; HR for OS=1.36 0.81–2.27, P=0.24). Grade ≥3 CNS treatment-related toxicity occurred in 5% of patients with BM and 3% without (P=0.43). Grade 5 treatment-related toxicity was seen in 5% of BM patients versus 2% without BM (P=0.31). Among 18 patients with BM who progressed, 1 (5.5%) had intra-cranial progression only, 12 (66.7%) had extra-cranial progression only, and 5 (27.8%) had both. In this rare tumor cohort treated with dual checkpoint blockade, patients with BM had similar response rates, survival outcomes, and toxicity profiles compared to those without BM. CNS-specific toxicity and progression patterns were also comparable.
Ahluwalia et al. (Fri,) studied this question.
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