401P - Utidelone in combination with etoposide and bevacizumab in HER2-negative breast cancer with brain metastasis (UTOBIA-BM): A prospective, single-arm, phase II trial

Background

Utidelone, a genetically engineered epothilone analogue, has been proved to be efficacious for advanced breast cancer. However, the effect of utidelone for breast cancer patients(pts) with brain metastasis has not been reported. This trial was to assess the efficacy and safety of utidelone in combination with etoposide and bevacizumab in HER2-negative breast cancer pts with brain metastasis.

Methods

HER2-negative breast cancer pts with brain metastasis were enrolled and Simon’s two-stage optimal trial design was used for this trial (NCT05781633). If more than 3 out of 13 pts show central nervous system (CNS) response, 30 more pts would be further enrolled. Utidelone (30mg/m², iv, d1-5), and etoposide (100mg/m², iv, d1-3) concurrently with bevacizumab (10mg/kg iv, d1) every 21 days for 6 cycles, with utidelone and bevacizumab maintenance until disease progression or unacceptable toxicity. The primary endpoint was CNS–objective response rate (ORR). Secondary endpoints include CNS-clinical benefit response (CBR), CNS-progression-free survival (PFS), ORR, PFS, CBR, overall survival (OS), and safety.

Results

17 female pts with a median age of 48 years (range 34-67) were enrolled from August 11, 2022 to March 22, 2023. 11 patients are evaluable for response with median cycles of 6 (2-8) , all of whom are still under treatment. CNS-ORR, CNS-CBR, ORR, CBR were 73% (8/11), 82% (9/11), 27% (3/11) and 55% (6/11), respectively, including a pt with PR for 8 cycles. PFS and OS have not been reached due to a short follow-up time. Therefore, the trial has met the criteria to enter the second stage. The major adverse event (AE) was peripheral neuropathy (PN), primarily classified as sensory. Grade 3 PN was seen in 9% (1/11) of the total patients. Most of the treatment-related AEs were grade 1 or 2 and were considered manageable and reversible. 1 pt experienced utidelone-related dose adjustment. No treatment-related death occurred.

Conclusions

Utidelone in combination with etoposide and bevacizumab has shown anti-tumor activity and manageable toxicity in breast cancer pts with brain metastasis, and a randomized control trial is warrantied.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Tianjin Science and Technology Funding (18ZXXYSY00070); Tianjin Municipal Education Commission Funding(2016YD03); Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-009A).

Disclosure

All authors have declared no conflicts of interest.