title: FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer.
abstract: OBJECTIVE
  To compare the effect of therapy with anastrozole versus a combination of fulvestrant and anastrozole in women in first relapse of endocrine-responsive breast cancer.
  
  
  METHODS
  Postmenopausal women, or premenopausal women receiving a gonadotropin-releasing hormone agonist, with estrogen receptor- and/or progesterone receptor-positive disease at first relapse after primary treatment of localized disease were open-label randomly assigned to a fulvestrant loading dose (LD) regimen followed by monthly injection plus 1 mg of anastrozole daily or to 1 mg of anastrozole daily alone. The primary end point was time to progression (TTP).
  
  
  RESULTS
  In all, 514 women were randomly assigned to fulvestrant plus anastrozole (experimental arm; n = 258) or anastrozole (standard arm; n = 256). Approximately two thirds had received adjuvant antiestrogens, but only eight individuals had received an aromatase inhibitor. Median TTP was 10.8 and 10.2 months in the experimental versus standard arm, respectively (hazard ratio [HR] = 0.99; 95% CI, 0.81 to 1.20; P = .91); median overall survival was 37.8 and 38.2 months, respectively (HR = 1.0; 95% CI, 0.76 to 1.32; P = 1.00). Incidences of prespecified adverse events (AEs) were similar. Hot flashes were more common in the experimental arm: 63 patients (24.6%) versus 35 patients (13.8%) in the standard arm (P = .0023). Death owing to AEs was reported in 11 (4.3%) and five patients (2.0%) in the experimental versus standard arm, respectively.
  
  
  CONCLUSIONS
  Fulvestrant (250 mg + LD regimen) in combination with anastrozole offered no clinical efficacy advantage over anastrozole monotherapy in this population of individuals with a relatively high proportion of previous adjuvant antiestrogen exposure.
authors.affiliation: Karolinska Institutet, Stockholm, Sweden. jonas.bergh@ki.se
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Per-Ebbe
authors.initials: PE
authors.lastname: Jönsson
authors.forename: Elisabet Kerstin
authors.initials: EK
authors.lastname: Lidbrink
authors.forename: Maureen
authors.initials: M
authors.lastname: Trudeau
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eiermann
authors.forename: Daniel
authors.initials: D
authors.lastname: Brattström
authors.forename: Justin P O
authors.initials: JP
authors.lastname: Lindemann
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D011960:Receptors, Estrogen / Q000378:metabolism; D012008:Recurrence; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D000077267:Fulvestrant; D000077384:Anastrozole; D004958:Estradiol