Sep 28

QP 08 - CNS Metastases and LMD: Patient Selection, Treatment Strategy and Outcomes

1045 - Pembrolizumab and Stereotactic Radiosurgery (SRS) of Selected Brain Metastases in Breast Cancer Patients

03:20pm - 03:25pm ET

Room 254

Presenter(s)

Fabiana Gregucci, MD - Weill Cornell Medical College, New York, NY

F. Gregucci¹, F. Talebi¹, K. Beal¹, E. Andreopoulou², M. Cristofanilli², M. Patel¹, L. Muller¹, A. Berliner¹, E. Lin³, and S. C. Formenti¹; ¹Department of Radiation Oncology, NewYork-Presbyterian/Weill Cornell Medicine, New York, NY, ²Weill Cornell Medical College, New York, NY, ³Weill Cornell Medical College/NewYork-Presbyterian Hospital, New York, NY

Purpose/Objective(s):

To evaluate the safety and preliminary intracranial efficacy of combining pembrolizumab with stereotactic radiosurgery (SRS) delivered to selected brain metastases, while assessing response in non-irradiated metastases.

Materials/Methods:

This prospective, non-randomized phase 1–2 trial (NCT03449238) enrolled breast cancer patients with =2 measurable brain metastases eligible for SRS. Selected metastases were chosen by treating radiation oncologist to receive SRS in 3–5 fractions, leaving =1 untreated lesion. Pembrolizumab was administered intravenously the day after SRS and every 3 weeks until progression or unacceptable toxicity. Intracranial response of non-irradiated metastases was assessed by MRI 8–16 weeks post-SRS using RANO criteria. Follow-up occurs every 3 weeks. According to statistical consideration if in the first 23 evaluable patients, there are 5 or more responses, an additional 18 evaluable patients will be enrolled.

Results:

From December 2018 to January 2026, 16 patients were evaluable (median age 53 years; range 25–78; 12 HR+/HER2–, 2 HER2+, 2 triple-negative). Median number of irradiated metastases was 4 (range 1–7), and non-irradiated metastases 1 (range 1–3). At 8–16 weeks, non-irradiated metastases showed partial response (PR) in 3/16, stable disease (SD) in 6/16, and progressive disease (PD) in 7/16 (disease control rate 53%).

Irradiated metastases achieved PR in 11/16 and SD in 5/16. Median follow-up was 52 weeks (range 12–156). Median overall survival was 82 weeks (95% CI 31–151), and intracranial progression-free survival was 16 weeks (95% CI 8–22). All 7 patients with PD in non-irradiated metastases subsequently received SRS. Treatment was generally well tolerated; one patient discontinued due to inflammatory arthritis.

Conclusion:

Selective irradiation of brain metastases combined with pembrolizumab is feasible and well tolerated. Meaningful early disease control in non-irradiated metastases (53% at 8–16 weeks) suggests potential out-of-field immune effects. These findings support further investigation of radiation–immunotherapy interactions, durability of response, and optimal patient selection in breast cancer brain metastases.