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

Fontein, D.B.Y.; Nortier, J.W.R.; Liefers, G.J.; Putter, H.; Meershoek-Klein Kranenbarg, E.; van den Bosch, J.; Maartense, E.; Rutgers, E.J.Th.; van de Velde, C.J.H.

doi:10.1016/j.ejso.2011.11.010

« Previous Next »European Journal of Surgical Oncology
Volume 38, Issue 2 , Pages 110-117, February 2012

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

D.B.Y. Fontein
- Department of Surgical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, The Netherlands
- Corresponding author. Tel.: +31 71 526 3500; fax: +31 71 526 6744.
J.W.R. Nortier
- Department of Medical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, The Netherlands
G.J. Liefers
- Department of Surgical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, The Netherlands
H. Putter
- Department of Medical Statistics, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, The Netherlands
E. Meershoek-Klein Kranenbarg
- Department of Surgical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, The Netherlands
J. van den Bosch
- Department of Medical Oncology, Albert Schweitzer Hospital, P.O. Box 444, 3300AK Dordrecht, The Netherlands
E. Maartense
- Department of Medical Oncology, Reinier de Graaf Hospital, P.O. Box 5011, 2600GA Delft, The Netherlands
E.J.Th. Rutgers
- Department of Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands
C.J.H. van de Velde
- Department of Surgical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, The Netherlands

Accepted 21 November 2011.

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.

Keywords: Non-compliance, Extended adjuvant endocrine therapy, Adverse events, Early stage breast cancer, Letrozole