Efficacy and toxicity of nivolumab and ipilimumab in rare cancer brain metastases: A multi-center basket trial analysis (NCI/SWOG S1609).

Abstract

2619 Background: Outcomes of patients with brain metastases (BM) treated with single or dual checkpoint inhibitors have been previously evaluated, showing similar intra-cranial and extra-cranial response rates and overall survival (OS). However, prior research has primarily focused on common tumor types such as melanoma and lung cancer. We report outcomes in patients with BM from the largest basket trial for rare cancers (N=684 evaluable patients) to evaluate efficacy and toxicity. Methods: 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 across >1000 sites. The protocol and consent were reviewed and approved by SWOG, the NCI, the NCI central institutional review board, and institutional review boards of participating sites. Efficacy and toxicity were assessed in patients with and without BM at enrollment. Progression-free survival (PFS), and OS were estimated using Kaplan-Meier methodology. Tumor response was evaluated per RECIST v1.1, toxicities were assessed using CTCAE v5.0. Hazard ratios (HR) with 95% confidence intervals (CI) and P-values were calculated to compare outcomes. Results: Similar response rates were observed in patients without BM (11%, n=707) compared to 10% in those with BM at enrollment (n=20). PFS and OS were comparable between patients with and without BM at enrollment (HR=1.29 [0.81-2.07], P=0.28; HR=1.36 [0.81-2.27], P=0.24, respectively). Grade ≥3 CNS treatment-related toxicity occurred in 3% of patients without BM versus 5% in those with BM (P=0.43). Similarly, Grade 5 treatment-related toxicity was observed in 2% of patients without BM compared to 5% in patients with BM (P=0.31). Among 18 patients with BM with progression, intra-cranial progression only was seen in 1 (5.5%) patient, while extra-cranial disease progression only in 12 (66.7%); 5 (27.8%) patients experienced concurrent intra- and extra-cranial disease progression. Conclusions: In this unique cohort of patients with rare tumors and BM receiving dual checkpoint inhibitor therapy, similar response rates and survival outcomes were observed in patients with or without BM at enrollment. No significant differences in CNS or non-CNS toxicity were noted. Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819. Clinical trial information: NCT02834013 . Clinical outcomes and cox regression analysis. Outcome No BM (n=707), n (%) BM (n=20), n (%) P-value Best RECIST Response 0.76 Confirmed CR/PR 81 (11.5) 2 (10) Unconfirmed CR/PR 22 (3.1) 0 (0) Clinical benefit (SD >6 mo) 97 (13.7) 3 (15) SD <6 mo or censored 123 (17.4) 1 (5) Progression/Failure 384 (54.3) 14 (70) PFS, HR (95% CI) UnivariateMultivariate 1.22 (0.77-1.93)1.29 (0.81-2.07) 0.39 0.28 OS, HR (95% CI) UnivariateMultivariate 1.23 (0.75-2.02)1.36 (0.81-2.27) 0.41 0.24