title: High non-compliance in the use of letrozole after 2.5 years of extended adjuvant endocrine therapy. Results from the IDEAL randomized trial.
abstract: OBJECTIVE
  The aim of this study was to investigate non-compliance to aromatase inhibitors and factors associated with early treatment discontinuation in the extended adjuvant setting.
  
  
  METHODS
  The IDEAL trial is a prospective, open-label phase-III trial comparing 2.5 with 5 years of extended adjuvant letrozole (LET) in hormone receptor positive (HR+) postmenopausal early breast-cancer patients after 5 years of adjuvant endocrine therapy (ET). The purpose of this study was to assess non-compliance in the first 2.5 years of extended adjuvant therapy. Non-compliance was defined as early discontinuation of LET for all reasons, excluding death or recurrence.
  
  
  RESULTS
  At 2.5 years, 1215 patients were included in the analysis. Overall non-compliance probability was 18.4%, of which 85.1% discontinued due to toxicities. Analyses showed that patients with prior sequential therapy were less likely to discontinue treatment than when treated with AI or TAM upfront (logrank p = 0.004). Longer treatment-free intervals also predicted more non-compliance (logrank p = 0.011). Age was not predictive of non-compliance (p = 0.571). Prior surgery (mastectomy vs breast conserving surgery), both with or without radiotherapy and/or chemotherapy were also not associated with early treatment discontinuation (p = 0.228 and p = 0.585 respectively). Although having fewer than four positive lymph nodes predicted more non-compliance (logrank p = 0.050), age, tumor type and locoregional treatment did not.
  
  
  CONCLUSIONS
  High non-compliance to extended ET was confirmed. Toxicities were the major reason for discontinuation, and this was not influenced by age. Longer treatment-free intervals and fewer positive lymph nodes predicted more non-compliance. Patients who underwent sequential therapy were least likely to discontinue extended adjuvant ET.
authors.affiliation: Department of Surgical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, The Netherlands. d.b.y.fontein@lumc.nl
authors.forename: D B Y
authors.initials: DB
authors.lastname: Fontein
authors.forename: J W R
authors.initials: JW
authors.lastname: Nortier
authors.forename: G J
authors.initials: GJ
authors.lastname: Liefers
authors.forename: H
authors.initials: H
authors.lastname: Putter
authors.forename: E
authors.initials: E
authors.lastname: Meershoek-Klein Kranenbarg
authors.forename: J
authors.initials: J
authors.lastname: van den Bosch
authors.forename: E
authors.initials: E
authors.lastname: Maartense
authors.forename: E J Th
authors.initials: EJ
authors.lastname: Rutgers
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077289:Letrozole; D008134:Long-Term Care; D015412:Mastectomy, Segmental; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance / Q000706:statistics & numerical data*; D011446:Prospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole