High non-compliance in the use of letrozole after 2.5 years of extended adjuvant endocrine therapy. Results from the IDEAL randomized trial

Eur J Surg Oncol. 2012 Feb;38(2):110-7. doi: 10.1016/j.ejso.2011.11.010. Epub 2011 Dec 14.

Abstract

Aims: 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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Antineoplastic Agents, Hormonal / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Confidence Intervals
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Letrozole
  • Long-Term Care
  • Mastectomy, Segmental
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Patient Compliance / statistics & numerical data*
  • Prospective Studies
  • Risk Assessment
  • Statistics, Nonparametric
  • Survival Rate
  • Time Factors
  • Treatment Outcome
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Nitriles
  • Triazoles
  • Letrozole