Editor’s Note: In recent years, systemic treatment options for HER2-positive breast cancer brain metastases have made meaningful progress, yet substantial unmet clinical needs remain. At the 2025 San Antonio Breast Cancer Symposium (SABCS), the team led by Professor Yan Min from Henan Cancer Hospital presented new research findings on systemic therapy for HER2-positive breast cancer brain metastases (Abstract No. PS5-01-13), which were selected for poster presentation. This work reflects the team’s continued and in-depth exploration in this challenging field. Oncology Frontier invited one of the study investigators, Associate Chief Physician Lü Huimin from Henan Cancer Hospital, to introduce and interpret the study.PS5-01-13 — Utidelone Plus Bevacizumab for the Treatment of HER2-Positive Breast Cancer Brain Metastases (U-BOMB-HER): A Multicenter, Single-Arm Phase II Study
Study Overview
Background Although novel HER2-targeted agents, including tyrosine kinase inhibitors (TKIs) and antibody–drug conjugates (ADCs), have demonstrated intracranial activity in patients with HER2-positive metastatic breast cancer and active brain metastases, patients who progress after TKI or ADC therapy still face major therapeutic challenges. Based on evidence of utidelone’s favorable penetration across the blood–brain barrier and the anti-edema effects of bevacizumab, this study aimed to evaluate the efficacy of their combination in HER2-positive breast cancer brain metastases after TKI failure (NCT05357417).
Methods This was a multicenter, single-arm phase II trial (NCT05357417) enrolling patients with newly diagnosed or progressive active brain metastases. The present report focuses on the HER2-positive cohort (U-BOMB-HER), which included patients with HER2-positive breast cancer brain metastases who had failed prior trastuzumab and TKI therapy. Patients received utidelone plus bevacizumab until disease progression or unacceptable toxicity. The primary endpoint was central nervous system objective response rate (CNS-ORR) assessed by RECIST 1.1. Secondary endpoints included CNS disease control rate (CNS-DCR), progression-free survival (PFS), CNS-PFS, overall survival (OS), and safety.
Results Between May 2022 and April 2025, 50 evaluable patients were enrolled, with a median age of 52 years. Baseline characteristics showed a median of three prior lines of systemic therapy. The distribution of brain metastases was as follows: single lesion in 14 patients, two lesions in 10 patients, and three or more lesions in 26 patients. Fifty-six percent of patients had not received prior radiotherapy, while 44 percent had progressed after radiotherapy. More than half of the patients (52 percent) had previously been treated with ADCs.
As of June 30, 2025, with a median follow-up of 14 months, the CNS-ORR was 54.0 percent and the CNS-DCR was 92.0 percent. The median PFS was 8.6 months (95% CI, 7.0–10.2), the median CNS-PFS was 11.0 months (95% CI, 8.4–13.6), and the median OS was 15.1 months (95% CI, 8.2–22.0).
The most common adverse events of any grade included peripheral neuropathy (96.0 percent), hematologic toxicities such as leukopenia (58.0 percent), neutropenia (50.0 percent), anemia (42.0 percent), and liver function abnormalities with elevated ALT or AST (52.0 percent). Grade 3 events were mainly neutropenia (16.0 percent) and hypertension (12.0 percent), with peripheral neuropathy occurring in 6.0 percent. No grade 4 or higher treatment-related adverse events were observed.
Conclusions The combination of utidelone and bevacizumab demonstrated substantial intracranial activity with a manageable safety profile in patients with HER2-positive breast cancer brain metastases who had progressed after TKI therapy. This regimen represents a promising systemic treatment option for this difficult-to-treat population.
Investigators’ Perspective
Despite encouraging intracranial activity observed with TKIs and anti-HER2 ADCs in HER2-positive breast cancer brain metastases, significant unmet needs remain after disease progression on these agents. To address this gap, our team initiated the U-BOMB-HER study to explore systemic treatment strategies for heavily pretreated patients.
This study innovatively combined utidelone, a microtubule inhibitor with good blood–brain barrier penetration, and bevacizumab, which can alleviate cerebral edema and improve the tumor microenvironment. The preliminary results show that this combination provides meaningful central nervous system antitumor activity and durable disease control in a highly refractory population, with an overall safety profile that is acceptable. These findings suggest the potential to extend overall survival in this group of patients.
Importantly, the study not only confirms the intracranial efficacy of chemotherapy combined with anti-angiogenic therapy in HER2-positive breast cancer brain metastases, offering a new option for patients who have failed TKI therapy, but also further supports the central role of systemic therapy in the comprehensive management of breast cancer brain metastases. The results lay a foundation for future exploration of more effective combination strategies and predictive biomarkers, and carry significant clinical value and developmental potential.
Yan Min, MD, PhD Department of Breast Surgery, Henan Cancer Hospital Deputy Director, Henan Breast Disease Diagnosis and Treatment Center
Lü Huimin, MD Department of Medical Oncology, Breast Cancer Diagnosis and Treatment Center Henan Cancer Hospital
