Phase II Clinical Study of Adebrelimab and Bevacizumab Combined With Cisplatin/Carboplatin in Patients With Triple-Negative Breast Cancer With Brain Metastases (ABC Study).

[PURPOSE] Brain metastases (BMs) of triple-negative breast cancer (TNBC) are lethal, often associated with a limited life span and lack of effective antitumor agents. Here we reported a triple combination therapy consisting of adebrelimab, bevacizumab, and cisplatin/carboplatin in BMs of TNBC.

[METHODS] This phase II clinical trial involved patients with TNBC with active BMs. Participants were administered with adebrelimab, bevacizumab, and cisplatin/carboplatin until disease progression or unacceptable toxic effects. The primary end point was the objective response rate in CNS (CNS-ORR) according to the Response Assessment in Neuro-Oncology BMs criteria, and the secondary end points included the clinical benefit rate in CNS (CNS-CBR), progression-free survival (PFS), overall survival (OS), the first progression site, and safety.

[RESULTS] A total of 35 patients were enrolled and treated, and the median lines of previous treatment were 2 (range, 0-4). The confirmed CNS-ORR was 77.1% (27/35, 95% CI, 59.9 to 89.6), and the CNS-CBR was 80.0% (28/35, 95% CI, 63.1 to 91.6). The median overall PFS was 8.3 months (95% CI, 5.8 to 11.5), whereas the median CNS-PFS was 10.3 months (95% CI, 7.4 to 14.3) and the median OS was 21.1 months (95% CI, 13.2 to not reached). Among the 28 patients who progressed, progression was intracranial-only in 32.1% (9/28) patients, extracranial-only in 35.7% (10/28) patients, and both in 32.1% (9/28) patients. The incidence of grade ≥3 treatment-related adverse events was 65.7% (23/35). Treatment-related serious adverse events occurred in five patients (14.3%), and no treatment-related deaths were reported.

[CONCLUSION] The combination of adebrelimab, bevacizumab, and cisplatin/carboplatin was the first regimen to demonstrate promising intracranial antitumor activity and prolonged PFS and CNS-PFS, along with a manageable safety profile, warranting further investigation.