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Purpose <p>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.</p> Methods <p>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.</p> Results <p>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&#xa0;months (95% confidence interval (CI): 0.95 – NA) and the median OS was 9.7&#xa0;months (95% CI: 3.6 – NA). The best observed response by RECIST 1.1 criteria was stable disease ≥ 24&#xa0;weeks in one participant (16.7%).</p> Conclusions <p>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.</p> Clinical Trial Registry Number <p><a href="https://www.clinicaltrials.gov">https://www.clinicaltrials.gov</a> NCT03483012.</p> <p>Trial Open to Accrual: 05/01/2018.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月7日

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  • Antonio Giordano,
  • Noah Graham,
  • Ayal A. Aizer,
  • Nabihah Tayob,
  • Alyssa M. Pereslete,
  • Jonathan D. Schoenfeld,
  • Jose Pablo Leone,
  • Raechel Davis,
  • Timothy K. Erick,
  • Erica L. Mayer,
  • Eric P. Winer,
  • Ian Krop,
  • Sara M. Tolaney,
  • Nancy U. Lin

摘要

Purpose

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.

Methods

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.

Results

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%).

Conclusions

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.

Clinical Trial Registry Number

https://www.clinicaltrials.gov NCT03483012.

Trial Open to Accrual: 05/01/2018.