A Phase III randomized trial finds that a new chemotherapy agent, eribulin mesylate (E7389, E), extends median overall survival by about 2.5 months among women with locally recurrent or metastatic breast cancer who had already been heavily treated with conventional therapies.

Worldwide, more than one million women a year are diagnosed with breast cancer.[1] Approximately 50 percent of women worldwide initially diagnosed with breast cancer are expected to develop recurrent or metastatic disease within 15 years of their first diagnosis.[2,3] Only one in five women with metastatic breast cancer survives longer than five years.[4] In the United States, an estimated 155,000 women are currently living with metastatic breast cancer, and that number is projected to increase to 162,000 by 2011.[5]

?Until now, there hasn?t been a standard treatment for women with such advanced breast cancer. For those who have already received all of the recognized treatments, these are promising results,? said lead author Christopher Twelves, MD, professor of clinical cancer pharmacology and oncology, and Head of the Clinical Cancer Research Groups at the Leeds Institute of Molecular Medicine and St. James?s Institute of Oncology in Leeds, U.K. ?These findings may establish eribulin as a new, effective option for women with heavily pre-treated metastatic breast cancer.?

A new Approach
Eribulin mesylate is a new type of (nontaxane) ?microtubule dynamics inhibitor? that affects cell division. The drug is a structurally-simplified, fully synthetic analog of the marine sponge (Lissodendoryx sp.) natural product halichondrin B. Eribulin inhibits microtubule dynamics via a mechanistically novel mode of action.

The international, multicenter trial, called EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice Versus E7389), is the first to compare eribulin mesylate to ?treatment of physician?s choice? in women with locally recurrent or metastatic breast cancer who had already received an average of four prior chemotherapy drugs, such as anthracyclines or taxanes. Because no single chemotherapy regimen is standard for these women, physicians chose which treatment to give patients in this study?s control arm, to reflect real-life choices.

Trial Design
Dr. Twelves and his colleagues compared overall survival among 762 patients with metastatic breast cancer who were randomized to receive either eribulin (508 women) or their physician?s choice of therapy (254 women), which was almost always another chemotherapy. The median survival for the eribulin group was significantly longer: 13.1 months versus 10.7 months. The study?s secondary endpoints (progression-free survival and objective response rate) also favored eribulin, which was generally well tolerated.

Other trials: NSCLC
The drug has previously been tested in a group of NSCLC patients. In An open-label, single-arm, Phase II study of eribulin conducted in patients with advanced NSCLC (ECOG of 0 or 1) eribulin demonstrated an increase in overall PR rate. Date of this study was presented during the 2007 Annual meeting of the American Society of Clinical Oncology (abstract 7546)

Oral Abstract Session: Breast Cancer-Metastatic
Lead author: Christopher Twelves, MD Leeds Institute of Molecular Medicine and St. James?s Institute of Oncology, Leeds, UK
Location: E Hall D1
Date: Tuesday, June 8, 2010 9:30 ? 9:45 AM, CDT
Abstract: CRA 1004
Title: A phase III study (EMBRACE) of eribulin mesylate versus treatment of physician?s choice in patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane.
Authors: C. Twelves, D. Loesch, J. L. Blum, L. T. Vahdat, K. Petrakova, P. J. Chollet, C. E. Akerele, S. Seegobin, J. Wanders, J. Cortes, on behalf of the Study 305 investigators

References:
1 Coughlin, S. Breast cancer as a global health concern. Cancer Epidemiology, October 2009; 33: 315-18.
2 Cardoso F and Castiglione M. Locally recurrent or metastatic breast cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Annals of Oncology, 2009; 20(4): iv15-iv18.
3 Jatoi I et al. Hazard rates of recurrence following diagnosis of primary breast cancer. Breast Cancer Research and Treatment, 2005; 89: 173-78.
4 Gonzalez-Angulo AM et al. Overview of Resistance to Systemic Therapy in Patients with Breast Cancer. Breast Cancer Chemosensitivity (Advances in Experimental Medicine and Biology, Vol. 608), 2007; 1-16.
5 AdvancedBC.org. Overcoming Isolation and Exposing Misconceptions. Bridging Gaps & Expanding Outreach for Metastatic Breast Cancer, September 2008. Available at advancedbe (last accessed 06/06/10).

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