Abstract
IMPORTANCE: Patients with ERBB2 (formerly HER2 or HER2/neu)-negative metastatic breast cancer (MBC) and brain metastases have poor prognosis, and effective treatment options are limited. OBJECTIVE: To investigate the activity and safety of utidelone plus bevacizumab in patients with ERBB2-negative MBC and active brain metastases. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized clinical trial was conducted at 5 hospitals in China. Adult patients with ERBB2-negative MBC who had untreated or progressive brain metastases were enrolled between May 5, 2022, and October 25, 2023. The data cutoff date was May 20, 2024; data were analyzed from September 15, 2022, to July 20, 2024. INTERVENTIONS: Patients received bevacizumab (15 mg/kg on day 1) and utidelone (30 mg/m2 on days 1-5) every 3 weeks until disease progression or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES: The primary end point was central nervous system (CNS) objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: A total of 47 female patients (median age, 53 years [IQR, 45-59 years]) were recruited. Of these, 35 patients had untreated brain metastases and 12 had brain metastases that had progressed after local radiotherapy. The CNS ORR was 42.6% (95% CI, 28.3%-57.8%) per RECIST version 1.1 and 40.4% (95% CI, 26.4%-55.7%) per Response Assessment in Neuro-Oncology Brain Metastases criteria. The median follow-up duration was 11.0 months (range, 2.3-23.6 months). The median progression-free survival (PFS) was 7.7 months (95% CI, 5.6-9.7), median CNS-PFS was 10.6 months (95% CI, 8.4 months to not reached), and median overall survival was 15.1 months (95% CI, 12.0 months to not reached). The most common grade 3 or higher treatment-emergent adverse events were decreased lymphocyte count in 5 patients (10.6%) and decreased white blood cell count in 3 patients (6.4%). No serious or fatal adverse events occurred. CONCLUSIONS AND RELEVANCE: The findings of this nonrandomized clinical trial suggest the potential of utidelone plus bevacizumab for the treatment of patients with ERBB2-negative MBC and active brain metastases. This treatment approach warrants further validation in a randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05357417.