Novel Injection Earns FDA ODD in Breast Cancer Brain Metastases

The blood-brain barrier can be penetrated with utidelone because of its physiochemical characteristic and insusceptibility to P-glycoprotein-mediated efflux. Moving forward, developers will research UTD1 in other brain tumors related to lung cancer and glioma.

The FDA has granted orphan drug designation to utidelone injectable (UTD1) for patients with breast cancer who have developed brain metastases, according to a press release from Biostar Pharma, Inc.¹

This designation was based on results from 2 phase 2 trials: UTOBIA-BM (NCT05781633) and an unnamed multicenter study (NCT05357417).^2,3 In the first trial, UTD1 was combined with etoposide and bevacizumab (Avastin), leading to a central nervous system (CNS) overall response rate (ORR) of 73% and a clinical benefit rate (CBR) of 91% in 17 patients with HER2-negative breast cancer brain metastases. In the second trial, utidelone plus bevacizumab was assessed. The progression-free survival (PFS) was 7.7 months, and the 12-month overall survival (OS) rate was 74.4% in 46 patients with HER2-negative breast cancer brain metastases.

The press release highlighted that the current median survival for those with breast cancer brain metastases is approximately 7.2 months and 3.5 months for those with triple-negative breast cancer brain metastases. Previously, macromolecular treatments have not been able to penetrate the blood-brain barrier, which has promoted low therapeutic efficacy. For breast cancer brain metastases, surgery and radiation therapy are the current standards of care.

The blood-brain barrier can be penetrated with utidelone because of its physiochemical characteristic and insusceptibility to P-glycoprotein-mediated efflux. Moving forward, developers will research UTD1 in other brain tumors related to lung cancer and glioma.

An estimated 43 patients were enrolled on the single-arm UTOPIA-BM study. Patients were given UTD1 at 30 mg/m² intravenously on days 1 to 5 for each 21-day cycle; etoposide at 30 mg/m² intravenously on days 1 to 3; and bevacizumab at 10 mg/kg on day 1. Between 4 and 6 cycles were given until a response or stable disease, with bevacizumab being used as maintenance therapy until toxicity or progression. Every 6 weeks, an MRI of the brain with contrast enhancement was performed; those with stable disease or a response were assessed every 9 weeks.

The primary end point was CNS ORR, and secondary end points included CNS CBR, CNS PFS, ORR, PFS, and OS.

To be enrolled on the trial, patients needed to be female, older than 18, have an ECOG performance status of 0 to 2, and have 1 measurable CNS lesion. Additionally, they needed to have untreated brain metastases from breast cancer that did not require local treatment, previously treated breast cancer brain metastases that have progressed after previous CNS treatment, and previous anti-HER2 therapy and tyrosine kinase inhibitor therapy for patients who had HER2-positive disease.

Patients who had other malignant tumors within the last 5 years, previous anti-tumor therapy within 4 weeks of entry, and previous use of the study treatments were ineligible for enrollment.

In the other phase 2 trial, patients received utidelone at 30 mg/m² on days 1 to 5 of each 3-week cycle and bevacizumab at 15 mg/kg on day 1.⁴ The study included 2 cohorts. In cohort 1, patients were included if they had HER2-negative advanced breast cancer with brain metastases and had received at least 1 prior anthracycline and taxane therapy. In cohort 2, patients were included if they had HER2-positive disease and had not seen a response from trastuzumab (Herceptin) or pyrotinib.

The primary end point was CNS ORR, with secondary end points including CNS ORR, CNS PFS, extracranial ORR, extracranial PFS, and OS.

Patients were eligible for enrollment if they had measurable disease and were previously treated with at least 1 anthracycline or taxane therapy and had prior unproven progression on bevacizumab or utidelone. Those with leptomeningeal metastases, the presence of effusions that cannot be controlled with drainage or another treatment, or participation on another clinical trial within 4 weeks of the study beginning were excluded from the trial.

References

1. 73% CNS ORR! FDA granted ODD to utidelone injectable (UTD1) from Biostar Pharma for the treatment of breast cancer brain metastasis. News release. Biostar Pharma, Inc. March 29, 2024. Accessed April 2, 2024. https://shorturl.at/mCR12
2. The efficacy and safety of eutideron, etoposide, and bevacizumab in patients with brain metastases from breast cancer. ClinicalTrials.gov. Updated March 23, 2023. Accessed April 2, 2024. https://shorturl.at/ntAFN
3. Shi Y, Wang P, Zhu Y, et al. Utidelone in combination with etoposide and bevacizumab in HER2-negative breast cancer with brain metastases (UTOBIA-BM): a prospective, single-arm, phase II trial. Ann Oncol. 2024;34(suppl 2):S349-S350. doi:10.1016/j.annonc.2023.09.578
4. Utidelone plus bevacizumab for advanced breast cancer with brain metastases. ClinicalTrials.gov. Updated September 16, 2022. Accessed April 1, 2024. https://shorturl.at/ertM4