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

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. [Copyright &y& Elsevier]