Ctim-01. nivolumab and stereotactic radiosurgery (srs) for patients with breast cancer brain metastases: long term results and cell free dna (cfdna) assessment from a non-randomized, open-label, phase ib study

Abstract BACKGROUND We hypothesized treatment with nivolumab and SRS would be feasible and well tolerated and may improve intracranial tumor control over SRS alone for breast cancer brain metastases. METHODS The study is a phase Ib trial of nivolumab and SRS for breast cancer brain metastases. Clinical trial information: NCT03807765. Key eligibility criteria include breast cancer brain metastases of all subtypes, age ≥ 18, ECOG ≤ 2 with ≥ 10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg IV) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. Blood was collected at baseline and q4 weeks. RESULTS A total of 12 patients were treated to 17 brain metastases. Breast cancer subtypes included triple negative (50%), HR+/HER2- (33%), and HR-/HER2+ (17%). Median follow-up from start of protocol therapy is 44 months. 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%. No cases of radionecrosis were noted. Most patients were noted to have an increase in cfDNA throughout study treatment, at week 5 compared to baseline (83%), week 25 compared to baseline (89%), and 100% at first follow-up. An increase in cfDNA 4 weeks post SRS was found to predict worse intracranial control (HR: 4.4; 95% CI: 1.1-18.5; p = 0.04). CONCLUSIONS Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. An increase in cfDNA 4 weeks post SRS was found to predict worse intracranial control and was eventually seen in all patients.