# A phase II study of atezolizumab in combination with stereotactic radiation for patients with triple-negative breast cancer and brain metastasis

## TL;DR

A clinical trial tested combining atezolizumab and stereotactic radiation for triple-negative breast cancer patients with brain metastases, finding it feasible but with poor outcomes.

## Contribution

This study evaluates the feasibility and outcomes of combining immunotherapy with stereotactic radiation in a specific patient population with limited treatment options.

## Key findings

- No dose-limiting toxicities were observed in the safety run-in phase.
- Median progression-free survival was 1.3 months and median overall survival was 9.7 months.
- Treatment-related adverse events occurred in 66.7% of patients but were all grade 2.

## Abstract

Triple-negative breast cancer (TNBC) patients with brain metastases have a poor prognosis and limited treatment options. Preclinical and clinical evidence suggests that radiotherapy may act synergistically with immune checkpoint inhibitors.

We conducted an open-label, single-arm, phase II study of atezolizumab plus stereotactic radiosurgery (SRS) in metastatic TNBC patients with brain metastases. The primary endpoint was progression-free survival (PFS) according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) bi-compartmental model. Secondary endpoints included extracranial objective response rate, overall survival (OS), and safety and tolerability. A safety run-in analysis for dose-limiting toxicity (DLT) was performed after the first 6 patients were enrolled and completed the assessment period.

Six patients were enrolled into the safety run-in phase between May 11, 2018 and October 24, 2019. No DLTs were observed, but the study was closed early due to slow accrual. Patients received a median of 2 atezolizumab cycles (range: 2—16), and SRS was administered to all 6 patients. Treatment-related adverse events (TRAEs) occurred in 4 participants (66.7%); all events were grade 2. The median bi-compartmental PFS was 1.3 months (95% confidence interval (CI): 0.95 – NA) and the median OS was 9.7 months (95% CI: 3.6 – NA). The best observed response by RECIST 1.1 criteria was stable disease ≥ 24 weeks in one participant (16.7%).

Concurrent SRS with atezolizumab was feasible in TNBC patients with brain metastases. However, disease outcomes were poor, and the development of effective therapies for these patients remains a significant unmet medical need.

https://www.clinicaltrials.gov NCT03483012.

Trial Open to Accrual: 05/01/2018.

The online version contains supplementary material available at 10.1007/s10549-026-07932-6.