Phase 1b Study of Stereotactic Radiation and Nivolumab in the Management of Metastatic Breast Cancer with Brain Metastases

Patients with breast cancer brain metastases represent a cohort with poor prognosis and a significant unmet clinical need. Standard-of-care treatments for patients with breast cancer brain metastases include local treatments, such as surgical resection and radiation treatment modalities that include stereotactic radiosurgery (SRS) or whole brain radiotherapy. Numerous preclinical studies have provided evidence that combining radiation therapy with immune checkpoint inhibition will improve response rates.1

At SABCS 2019, the authors presented the clinical trial design for treatment with nivolumab and SRS to determine if this combination will be feasible, well tolerated, and whether it improves intracranial tumor control rates compared with SRS alone.2 The study is designed as a prospective, single-arm, nonrandomized, open-label, phase 1b trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Treatment will be initiated with nivolumab 480 mg IV every 4 weeks. The initial dose of nivolumab will be followed 1 week later by SRS at sites of brain metastases or postoperative cavities. Patients will be allowed to continue endocrine and HER2-targeted therapies.

The primary objective of the study will be to evaluate the safety and feasibility of nivolumab and SRS to sites of brain metastases. Secondary objectives include evaluation of intracranial progression-free survival, extracranial progression-free survival, overall survival, local control, and distant brain control. Correlative aims include assessing blood and tissue biomarkers (ie, PD-L1, mutation burden, T-cell receptor repertoire) for possible association with clinical benefit. This study was open at the time of SABCS 2019 with 4 patients enrolled at the time of submission. A total of 12 patients will be enrolled.


  1. Berghoff AS, et al. ASCO Educ Book. 2016;36:e116-e122.
  2. Ahmed KA, et al. SABCS 2019. Abstract OT3-10-01.

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