title: Eribulin mesylate for the treatment of patients with refractory metastatic breast cancer: use of a "physician's choice" control arm in a randomized approval trial.
abstract: This work describes the considerations that led to the approval by the U.S. Food and Drug Administration (FDA), on November 15, 2010, of eribulin mesylate (Halaven; Eisai, Inc.) for the treatment of patients with refractory metastatic breast cancer. The FDA review focused primarily on the results of a single randomized, open-label, multicenter trial of 762 patients with refractory locally advanced or metastatic breast cancer. The patients were randomized to receive eribulin or any single-agent treatment of the physician's choice, selected prior to randomization. The FDA's approval of eribulin mesylate was based on demonstration of a statistically significant prolongation of overall survival (OS) in patients who had been randomized to receive eribulin. The median OS was 13.1 months in the eribulin arm compared with 10.6 months in the control arm [HR 0.81 (95% CI, 0.66-0.99); P = 0.041]. Treatment with eribulin did not show a statistically significant treatment effect [HR 0.87 (95% CI, 0.71-1.05)] on progression-free survival as determined by independent review. This approval highlights the appropriate use of an innovative trial design and shows that improvement in OS is an achievable endpoint in the setting of advanced breast cancer. On the basis of the different conclusions arising from the OS and progression-free survival results, investigators should consider using OS as a primary endpoint in clinical trials for refractory breast cancer.
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA. martha.donoghue@fda.hhs.gov
authors.forename: Martha
authors.initials: M
authors.lastname: Donoghue
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Lemery
authors.forename: Weishi
authors.initials: W
authors.lastname: Yuan
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.forename: Stacy
authors.initials: S
authors.lastname: Shord
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Anshu
authors.initials: A
authors.lastname: Marathe
authors.forename: Lori
authors.initials: L
authors.lastname: Kotch
authors.forename: Josephine
authors.initials: J
authors.lastname: Jee
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: William M
authors.initials: WM
authors.lastname: Adams
authors.forename: Vaishali
authors.initials: V
authors.lastname: Jarral
authors.forename: Anne
authors.initials: A
authors.lastname: Pilaro
authors.forename: Richard
authors.initials: R
authors.lastname: Lostritto
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Gootenberg
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D017277:Drug Approval; D005260:Female; D005663:Furans / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000009:adverse effects / Q000627:therapeutic use*; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic; D019233:Retreatment; D014481:United States; D014486:United States Food and Drug Administration; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D007659:Ketones; C490954:eribulin; D000095662:Polyether Polyketides