Nivolumab and stereotactic radiosurgery for patients with breast cancer brain metastases: long-term results and biomarker analysis from a non-randomized, open-label, phase Ib study
Kamran A. Ahmed, Younchul Kim, Sungjune Kim, Min Wang, Michelle DeJesus, John A. Arrington, Aixa Soyano, Avan Armaghani, Ricardo Costa, Loretta Loftus, Marilin Rosa, Jimmy J. Caudell, Roberto Díaz, Arnold B. Etame, Nam Tran, Hatem Soliman, Brian J. Czerniecki, Peter Forsyth, Ya-Yu Tsai, Hyo S. Han
Abstract
BACKGROUND: We hypothesized treatment with nivolumab and stereotactic radiosurgery (SRS) would be feasible, well tolerated, and may improve intracranial tumor control over SRS alone for breast cancer brain metastases (BCBM). METHODS: The study is a phase Ib trial of nivolumab and SRS for BCBM. CLINICAL TRIAL INFORMATION: NCT03807765. Key eligibility criteria include BCBM of all subtypes, age ≥18, Eastern Cooperative Oncology Group Performace Status (ECOG-PS)≤2 with ≤10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg intravenously) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. Blood was collected at baseline and every 4 weeks for flow cytometry and cell-free DNA (cfDNA) assessment. RESULTS: A total of 12 patients received SRS to 17 brain metastases. Breast cancer subtypes included triple negative (50%), hormone receptor (HR)+/HER2- (33%), and HR-/HER2+ (17%). Median follow-up from start of protocol therapy is 56 months. No cases of radionecrosis were noted. Two lesions were noted to undergo local failure, both pathologically confirmed, for a 12-month local control of 94%. Median distant intracranial control was 7.4 months with a 12-month control rate of 33%. Median systemic progression-free survival was 7.7 months with a 12-month rate of 42%. Median overall survival (OS) was 24.7 months with a 12-month OS of 75%. Most patients were noted to have an increase in cfDNA throughout study treatment, at week 5 compared with baseline (83%), week 25 compared with baseline (89%), and 100% at first follow-up. Intracranial control was associated with lower levels of CD4 regulatory T cells (Treg) (p=0.03) and higher levels of CD4 T effector memory (p=0.04). CONCLUSIONS: Nivolumab and SRS is a safe and feasible treatment option in BCBM. Long-term follow-up revealed no cases of radiation necrosis. TRIAL REGISTRATION NUMBER: NCT03807765.