title: Sequential treatment with exemestane and non-steroidal aromatase inhibitors in advanced breast cancer.
abstract: BACKGROUND
  The steroidal aromatase inactivator exemestane has demonstrated activity after prior failure of non-steroidal aromatase inhibitors (including third-generation inhibitors letrozole and anastrozole) in postmenopausal women with advanced breast cancer. If exemestane is used as first anti-aromatase agent, however, it is unclear whether patients can still benefit from letrozole or anastrozole after progression.
  
  
  METHODS
  Postmenopausal patients with advanced, hormone receptor-positive or -unknown breast cancer were eligible for this study. Patients with no prior exposure to anti-aromatase drugs received exemestane, 25 mg daily, as first anti-aromatase agent. At the time of progression, patients were crossed-over to anastrozole or letrozole if further endocrine therapy was considered appropriate. Patients with prior exposure to anti-aromatase agents were also included in the study, and were given anastrozole or letrozole if they had previously received exemestane, or exemestane if they had previously received anastrozole or letrozole. The primary endpoint of the study was the clinical benefit rate (complete response + partial response + stabilization of disease for >or=24 weeks).
  
  
  RESULTS
  Forty patients received exemestane 25 mg daily as first anti-aromatase agent, with a CB rate of 67.5% (95% CI 52.9-82.0%) and a median time to progression (TTP) of 9.6 months. In 18 patients, letrozole (n = 17) or anastrozole (n = 1) were used after failure of exemestane: the CB rate was 55.6% (95% CI 32.6-78.5%) with a median TTP of 9.3 months. In 23 patients, exemestane was used after failure of letrozole or anastrozole: the CB rate was 43.5% (95% CI 23.2-63.7%) with a median TTP of 5.1 months.
  
  
  CONCLUSIONS
  Our study confirms that exemestane is active after prior failure of letrozole or anastrozole. We have also shown that patients can receive exemestane as their first anti-aromatase agent and still benefit from letrozole or anastrozole after progression. This suggests that the partial non-cross resistance between steroidal and non-steroidal anti-aromatase agents is independent of the sequence employed.
authors.affiliation: South West Wales Cancer Institute, Swansea, United Kingdom. gianfilippo.bertellli@swansea-tr.wales.nhs.uk
authors.forename: Gianfilippo
authors.initials: G
authors.lastname: Bertelli
authors.forename: Ornella
authors.initials: O
authors.lastname: Garrone
authors.forename: Marco
authors.initials: M
authors.lastname: Merlano
authors.forename: Marcella
authors.initials: M
authors.lastname: Occelli
authors.forename: Laura
authors.initials: L
authors.lastname: Bertolotti
authors.forename: Federico
authors.initials: F
authors.lastname: Castiglione
authors.forename: Fiorella
authors.initials: F
authors.lastname: Pepi
authors.forename: Ornella
authors.initials: O
authors.lastname: Fusco
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Mastro
authors.forename: Robert C F
authors.initials: RC
authors.lastname: Leonard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000730:Androstadienes / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016001:Confidence Intervals; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077289:Letrozole; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage; D017698:Postmenopause; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane