Phase III Trials of Eribulin Mesylate (E7389) in Extensively Pretreated Patients With Locally Recurrent or Metastatic Breast Cancer

Eribulin mesylate (E7389) is a nontaxane microtubule dynamics inhibitor with a novel mechanism of action. In preclinical 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, including 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 being 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.