Rationale฀and฀Background Eribulin mesylate (E7389) is a structurally simplified, synthetic analogue of the marine natural product halichondrin B. Eribulin is a nontaxane microtubule dynamics inhibitor with potent antican- cer effects in preclinical models of a variety of tumor types, includ- ing breast cancer. 1-4 Eribulin has a mechanism of action distinct from other agents that target tubulin 3,5-7 and, for this as well as other reasons, may be effective in patients whose disease is resistant to other tubulin-targeting agents. In preclinical studies, eribulin retained activity in cell lines that were paclitaxel resistant as a result of β-tubulin mutations. 8 Following 3 phase I studies, 9-11 2 phase II studies 12,13 of eribulin in extensively pretreated patients with locally advanced or metastatic breast cancer have been completed. These trials showed that eribulin was therapeutically active, had a manageable toler- ability profile, and was associated with a low incidence of clini- cally significant peripheral neuropathy. Based on these encouraging results, 2 randomized, comparator-controlled phase III studies were initiated in patients with locally advanced/recurrent or meta- static breast cancer previously treated with an anthracycline and a taxane. Study E7389-G000-305 (Study 305, the EMBRACE study; NCT00388726) compares eribulin with the treatment of the physician’s choice. Study E7389-G000-301 (Study 301; Abstract Phase III Trials of Eribulin Mesylate (E7389) in Extensively Pretreated Patients With Locally Recurrent or Metastatic Breast Cancer Chris Twelves, 1 Javier Cortes, 2 Linda T. Vahdat, 3 Jantien Wanders, 4 Corina Akerele, 5 Peter A. Kaufman 6 Eribulin mesylate (E7389) is a nontaxane microtubule dynamics inhibitor with a novel mechanism of action. In pre- clinical studies, it has activity in a variety of in vivo tumor model types, including breast cancer. Following promising results from phase I and phase II studies in patients with breast cancer, 2 open-label, randomized, controlled, parallel- group phase III studies have been initiated, and enrollment has been completed. Both study populations comprise patients with locally advanced/recurrent or metastatic disease pretreated with several chemotherapy regimens, in- cluding an anthracycline and a taxane. In Study 305, eribulin is being evaluated as late-line therapy. The primary objective is to compare overall survival (OS) between eribulin monotherapy and treatment of the physician’s choice, and progression-free survival (PFS) is one of the secondary objectives. The 762 patients enrolled in Study 305 were randomized in a 2:1 ratio to receive either eribulin or treatment of the physician’s choice. In Study 301, eribulin is be- ing assessed as second-line therapy, and the primary objective is to compare eribulin and capecitabine in terms of OS and PFS. Secondary objectives include assessments of response data, duration of response, quality of life, pain intensity, analgesic consumption, and assessment of pharmacokinetic/pharmacodynamic relationships for eribulin. In Study 301, the 1102 patients enrolled were randomized to receive either eribulin or capecitabine (approximately 550 patients in each arm). Tumor assessments are carried out every 8 weeks in Study 305, and every 2 cycles (each of 3 weeks’ duration) in Study 301. Safety is also assessed in both studies. Clinical Breast Cancer, Vol. 10, No. 2, 160-163, 2010; DOI: 10.3816/CBC.2010.n.023 Keywords: Capecitabine, EMBRACE, Microtubule dynamics inhibitor, Study design, Treatment of physician’s choice Current฀Trial Trial Numbers/Registration Dates: NCT00388726, October 13, 2006; NCT00337103, June 13, 2006. 1 Leeds Institute of Molecular Medicine, St. James University Hospital, Leeds, United Kingdom 2 Vall d’Hebron University Hospital, Barcelona, Spain 3 Weill Cornell Medical College, New York, NY 4 Eisai Ltd., Hatfield, Hertfordshire, United Kingdom 5 Eisai Inc., Woodcliff Lake, NJ 6 Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH Submitted: Jan 21, 2010; Accepted: Jan 25, 2010; Epub: Mar 5, 2010 Address for correspondence: Chris Twelves, MD, Leeds Institute of Molecular Medicine & St. James’s Institute of Oncology, Level 4, Bexley Wing, St. James’s University Hospital, Beckett St, Leeds, LS9 7TF, UK Fax: 44-0-113-206-8474; e-mail: c.j.twelves@leeds.ac.uk This summary may include the discussion of investigational and/or unlabeled uses of drugs and/or devices that may not be approved by the FDA. Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1526-8209, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA. www.copyright.com 978-750-8400. 160 | Clinical Breast Cancer April 2010