Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): A phase 3 open-label randomised study
Abstract
Background Treatments with survival benefit are greatly needed for women with heavily pretreated metastatic breast cancer. Eribulin mesilate is a non-taxane microtubule dynamics inhibitor with a novel mode of action. We aimed to compare overall survival of heavily pretreated patients receiving eribulin versus currently available treatments.Methods In this phase 3 open-label study, women with locally recurrent or metastatic breast cancer were randomly allocated (2:1) to eribulin mesilate (1·4 mg/m(2) administered intravenously during 2-5 min on days 1 and 8 of a 21-day cycle) or treatment of physician's choice (TPC). Patients had received between two and five previous chemotherapy regimens (two or more for advanced disease), including an anthracycline and a taxane, unless contraindicated. Randomisation was stratified by geographical region, previous capecitabine treatment, and human epidermal growth factor receptor 2 status. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00388726.Findings 762 women were randomly allocated to treatment groups (508 eribulin, 254 TPC). Overall survival was significantly improved in women assigned to eribulin (median 13·1 months, 95% CI 11·8-14·3) compared with TPC (10·6 months, 9·3-12·5; hazard ratio 0·81, 95% CI 0·66-0·99; p=0·041). The most common adverse events in both groups were asthenia or fatigue (270 [54%] of 503 patients on eribulin and 98 [40%] of 247 patients on TPC at all grades) and neutropenia (260 [52%] patients receiving eribulin and 73 [30%] of those on TPC at all grades). Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in 24 (5%) of 503 patients.Interpretation Eribulin showed a significant and clinically meaningful improvement in overall survival compared with TPC in women with heavily pretreated metastatic breast cancer. This finding challenges the notion that improved overall survival is an unrealistic expectation during evaluation of new anticancer therapies in the refractory setting.Funding Eisai.
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Eribulin, a truncated synthetic version of halichondrin B, derived from the sponge Halichondria okadai, has clinically potential activity against pretreated metastatic breast cancer cells.
“Eribulin, a truncated synthetic version of halichondrin B, derived from the sponge Halichondria okadai [149], has clinically potential activity against pretreated metastatic breast cancer cells [150,151].”
From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [151]
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- Authors
- Cortes, J., O'Shaughnessy, J., Loesch, D., Blum, J. L., Vahdat, L. T., Petrakova, K., Chollet, P., Manikas, A., Diéras, V., Delozier, T., Vladimirov, V., Cardoso, F., Koh, H., Bougnoux, P., Dutcus, C. E., Seegobin, S., Mir, D., Meneses, N., Wanders, J., & Twelves, C.
- Affiliations
- Caris Life Sciences (United States) (US)
- Texas Oncology (US)
- Weill Cornell Medicine (US)
- Centre Jean Perrin (FR)
- City Clinical Oncology Center (RU)
- Centre François Baclesse (FR)
- Pyatigorsk Oncology Center (RU)
- Kaiser Permanente (US)
- Hôpital Bretonneau (FR)
- Eisai (United States) (US)
- Eisai (United Kingdom) (GB)
- University of Leeds (GB)
- Corresponding author
- Twelves, Chris
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 377
- Issue
- 9769
- Pages
- 914-923
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2127152525
- Cited by
- 1,094
- References
- 31
- Citations by year
- 2026: 34 · 2025: 49 · 2024: 58 · 2023: 68 · 2022: 64 · 2021: 95 · 2020: 82 · 2019: 76 · 2018: 100 · 2017: 92 · 2016: 76 · 2015: 81 · 2014: 69 · 2013: 43 · 2012: 65
- FWCI
- 34.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- Eisai
- Topics
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- metastatic breast cancer, heavily pretreated patients, overall survival, microtubule dynamics inhibitor, peripheral neuropathy, neutropenia
- MeSH terms
- Polyether Polyketides, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Breast Neoplasms, Female, Furans, Humans, Ketones, Middle Aged, Neoplasm Metastasis, Survival Rate, Disease-Free Survival
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