title: Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group.
abstract: OBJECTIVE
  To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer.
  
  
  METHODS
  Nine hundred seven patients were randomly assigned letrozole 2.5 mg once daily (453 patients) or tamoxifen 20 mg once daily (454 patients). Patients had estrogen receptor- and/or progesterone receptor-positive tumors, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, rate and duration of clinical benefit, time to treatment failure (TTF), overall survival, and tolerability.
  
  
  RESULTS
  TTP was significantly longer for letrozole than for tamoxifen (median, 41 v 26 weeks). Treatment with letrozole reduced the risk of progression by 30% (hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P =.0001). TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole (median, 40 v 25 weeks). ORR was higher for letrozole (30% v 20%; P =.0006), as was the rate of clinical benefit (49% v 38%; P =.001). Survival data are currently immature and not reported here. Both treatments were well tolerated.
  
  
  CONCLUSIONS
  Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer.
authors.affiliation: Rigshospitalet, Copenhagen, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Mouridsen
authors.forename: M
authors.initials: M
authors.lastname: Gershanovich
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: R
authors.initials: R
authors.lastname: Pérez-Carrión
authors.forename: C
authors.initials: C
authors.lastname: Boni
authors.forename: A
authors.initials: A
authors.lastname: Monnier
authors.forename: J
authors.initials: J
authors.lastname: Apffelstaedt
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.forename: H P
authors.initials: HP
authors.lastname: Sleeboom
authors.forename: F
authors.initials: F
authors.lastname: Jänicke
authors.forename: A
authors.initials: A
authors.lastname: Pluzanska
authors.forename: M
authors.initials: M
authors.lastname: Dank
authors.forename: D
authors.initials: D
authors.lastname: Becquart
authors.forename: P P
authors.initials: PP
authors.lastname: Bapsy
authors.forename: E
authors.initials: E
authors.lastname: Salminen
authors.forename: R
authors.initials: R
authors.lastname: Snyder
authors.forename: M
authors.initials: M
authors.lastname: Lassus
authors.forename: J A
authors.initials: JA
authors.lastname: Verbeek
authors.forename: B
authors.initials: B
authors.lastname: Staffler
authors.forename: H A
authors.initials: HA
authors.lastname: Chaudri-Ross
authors.forename: M
authors.initials: M
authors.lastname: Dugan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077289:Letrozole; D016015:Logistic Models; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D017698:Postmenopause; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole