title: Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT.
abstract: OBJECTIVE
  The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR+) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure.
  
  
  METHODS
  Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR+ advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily.
  
  
  RESULTS
  A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane (n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups (hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate (7.4% v 6.7%; P = .736) and clinical benefit rate (32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant.
  
  
  CONCLUSIONS
  Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency, University of British Columbia, 600 West 10 Avenue, Vancouver, BC, Canada. schia@bccancer.bc.ca
authors.forename: Stephen
authors.initials: S
authors.lastname: Chia
authors.forename: William
authors.initials: W
authors.lastname: Gradishar
authors.forename: Louis
authors.initials: L
authors.lastname: Mauriac
authors.forename: Jose
authors.initials: J
authors.lastname: Bines
authors.forename: Frederic
authors.initials: F
authors.lastname: Amant
authors.forename: Miriam
authors.initials: M
authors.lastname: Federico
authors.forename: Luis
authors.initials: L
authors.lastname: Fein
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.forename: Aman
authors.initials: A
authors.lastname: Buzdar
authors.forename: John F R
authors.initials: JF
authors.lastname: Robertson
authors.forename: Adam
authors.initials: A
authors.lastname: Brufsky
authors.forename: Kurt
authors.initials: K
authors.lastname: Possinger
authors.forename: Pamela
authors.initials: P
authors.lastname: Rennie
authors.forename: Francisco
authors.initials: F
authors.lastname: Sapunar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lowe
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
mesh_terms: D000730:Androstadienes / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D004311:Double-Blind Method; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D053208:Kaplan-Meier Estimate; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010919:Placebos; D017698:Postmenopause; D011788:Quality of Life; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D010919:Placebos; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; C056516:exemestane