Editor’s Note: The 2025 ASCO Annual Meeting is currently in full swing across the Pacific, and several China-led clinical studies in breast cancer have captured significant international attention. Among them, Professor Yehui Shi from Tianjin Medical University Cancer Institute and Hospital presented data from a Phase II prospective single-arm study investigating a novel triplet regimen of Utidelone, Etoposide, and Bevacizumab in patients with HER2-negative breast cancer brain metastases.This study addresses the current lack of effective systemic treatments for HER2-negative brain metastases, a particularly challenging subtype where standard therapies offer limited benefit due to the restrictive nature of the blood-brain barrier (BBB). The innovative combination demonstrated impressive outcomes: a central nervous system objective response rate (CNS-ORR) of 67.6%, a CNS clinical benefit rate (CNS-CBR) of 88.2%, and a breakthrough median CNS progression-free survival (CNS-PFS) of 15 months. These results represent a potential new treatment pathway and highlight the strong clinical value of this combination.
Following the presentation, Oncology Frontier invited Prof. Yehui Shi to offer a deeper analysis of the study results and their broader significance.
Oncology Frontier: To start, could you briefly introduce the background of this study and share the key findings you presented at the conference?
Prof. Yehui Shi, Tianjin Medical University Cancer Institute and Hospital: Brain metastasis from breast cancer is the second most common cause of intracranial metastatic disease, second only to lung cancer. Compared with HER2-positive breast cancer—which benefits from a range of anti-HER2 therapies—patients with HER2-negative breast cancer and brain metastases have very limited treatment options. Moreover, due to the presence of the blood-brain barrier (BBB), systemic therapies often fail to achieve satisfactory results. Currently, major clinical guidelines do not provide specific recommendations for systemic treatment in HER2-negative breast cancer patients with brain metastases.
Utidelone has been shown to penetrate the blood-brain barrier, as demonstrated by preclinical drug distribution studies and supported by several clinical trials. Based on this, we designed a Phase II prospective single-arm study to evaluate the efficacy and safety of Utidelone in combination with Etoposide and Bevacizumab for treating HER2-negative breast cancer patients with brain metastases. The goal was to explore whether this triplet regimen could offer a new, effective systemic treatment option for this underserved population.
At this year’s ASCO meeting, I presented the interim analysis of our study. Among the 34 patients enrolled, 11 had triple-negative breast cancer (TNBC) and 23 had luminal-type breast cancer. The median age was 52 years (range: 34–74), and the median number of prior lines of therapy was three.
As of December 2, 2024, with a median follow-up of 11.5 months, the central nervous system objective response rate (CNS-ORR) reached 67.6%, and the CNS clinical benefit rate (CNS-CBR) was 88.2%. In terms of survival outcomes, we observed a median progression-free survival (PFS) of 6 months (95% CI: 4.265–7.735 months). Notably, the median CNS progression-free survival (CNS-PFS) reached 15 months (95% CI: 6.760–23.240 months), which was significantly longer than the overall PFS—highlighting the CNS-specific benefit and offering patients a more effective treatment option.
The primary adverse event observed was peripheral neuropathy, with Grade 3 events (mainly sensory) occurring in 8.8% of patients (3 out of 34). Most treatment-related adverse events were Grade 1 or 2 and were considered manageable and reversible.
Oncology Frontier: In the current landscape of treatment options for patients with HER2-negative breast cancer brain metastases, what do you consider to be the most innovative aspects of this study’s regimen—Utidelone combined with Etoposide and Bevacizumab ? As a novel microtubule inhibitor, what key role do you believe Utidelone plays within this combination therapy?
Prof. Yehui Shi, Tianjin Medical University Cancer Institute and Hospital: The greatest innovation of this regimen lies in the use of a three-drug combination approach. Given the presence of both intracranial and extracranial tumor burden in these patients, treatment needs to not only control brain metastases but also effectively address extracranial lesions, such as those in the liver, lungs, bones, and lymph nodes.
Utidelone was previously approved in China for use in combination with capecitabine for patients with recurrent or metastatic breast cancer who had been treated with an anthracycline and/or taxane. In this study, we replaced capecitabine with Etoposide because capecitabine is a commonly used agent that many patients had already received in earlier lines of therapy. Etoposide, on the other hand, is less frequently used in later-line breast cancer treatment, making its combination with Utidelone both effective and novel. The final results showed a high response rate and prolonged duration of response.
I believe Utidelone plays a central role in this regimen. Research has shown that Utidelone can penetrate the blood-brain barrier, and its concentration in intracranial metastatic tumors is significantly elevated—this represents another key innovation of the study.
Oncology Frontier: The study results showed a CNS objective response rate (CNS-ORR) of 67.6%, a CNS clinical benefit rate (CNS-CBR) of 88.2%, and a median CNS progression-free survival (CNS-PFS) of 15 months. Compared with existing treatment options, what is the significance of these findings? How do you view the dual value of this regimen in both extending survival and improving patients’ quality of life?
Prof. Yehui Shi, Tianjin Medical University Cancer Institute and Hospital: Based on a comparison with previously published data, the CNS objective response rate (CNS-ORR) achieved with this three-drug combination is the highest reported to date, and patients also experienced the longest progression-free survival. These findings bring renewed hope for improved survival in patients with HER2-negative breast cancer brain metastases.
Importantly, the patients enrolled in our study were relatively heavily pretreated, with prior lines of therapy ranging from first-line to as many as seven lines, and an average of three lines. Despite this, they still achieved favorable survival outcomes, which offers meaningful guidance for future clinical practice.
This regimen provides dual value in both prolonging survival and improving quality of life. The high response rate and prolonged duration of response contribute to extended survival, while the regimen’s relative safety and manageability further support improvements in patients’ quality of life. These aspects offer valuable direction for future treatment strategies.
Chief Physician Director, Department of Medical Oncology (Breast Cancer), Tianjin Medical University Cancer Institute and Hospital
Academic and Professional Appointments:
- Executive Member, Breast Cancer Committee, Chinese Anti-Cancer Association
- Executive Member, Clinical Research Committee, Chinese Society for Medical Biotechnology
- Executive Member, Chemotherapy Committee, Chinese Medical Education Association
- Executive Member, Breast Disease Committee, Chinese Medical Education Association
- Chair, Committee on Clinical Trials of Antitumor Drugs, Tianjin Anti-Cancer Association
- Vice Chair, Clinical Trial Branch, Tianjin Medical Association
- Vice Chair, Ethics Review Committee for Clinical Trials, Tianjin Pharmaceutical Association
- Chair-elect, Chemotherapy Committee, Tianjin Anti-Cancer Association
