Low Adherence to Upfront and Extended Adjuvant Letrozole Therapy among Early Breast Cancer Patients in a Clinical Practice Setting

Abstract

Objective: The aim of this study was to investigate the prevalence and causes of early discontinuation and non-adherence to upfront and extended adjuvant letrozole therapy in breast cancer patients. Methods: Adherence was assessed using medical charts and longitudinal pharmacy records of 609 patients who initiated adjuvant letrozole between January 2002 and April 2011. A Cox proportional hazards regression model was adopted to identify potential predictors of non-adherence. Results: The overall adherence rate after 1 year of therapy was 79.5%, with cumulative rates declining to 63.7% after 3 years and 57.1% after 5 years. A significantly lower rate of adherence in the extended adjuvant group was observed compared with the upfront adjuvant group (49.0 vs. 72.5%, p < 0.001). Adverse events (50.4%) were the major cause of early discontinuation, with musculoskeletal pain (73.2%) being the single most cited reason. Additional factors correlating with non-adherence in the upfront adjuvant group included a delay in initiation of adjuvant hormone therapy, breast-conserving surgery, calcium supplements, bisphosphonate therapy and concomitant medication for co-morbidity. Conclusions: We observed that approximately 57% of patients fully adhered to letrozole therapy over a 5-year treatment period, and that the adherence to extended letrozole was meaningfully lower than the upfront adjuvant letrozole in a clinical practice setting.

Barriers and facilitators of adjuvant hormone therapy adherence and persistence in women with breast cancer: a systematic review

“…Nine studies showed lower odds of adherence for women under the age of 40/50 years, 9 , 23 , 28 , 31 , 33 , 34 , 38 , 39 , 58 one study found the opposite, 59 and three studies showed no significant effects. Six studies found that older women (>65/75 years) were less likely to be adherent.…”

“…The majority of clinical factors showed no consistent associations with adherence or showed mixed results (eg, tumor size, previous chemotherapy and lymph node status). Switching between HTs was associated with decreased adherence in seven studies 23 , 28 , 33 – 37 and increased adherence in three studies. 8 , 38 , 39 The majority of articles did not specify the direction of switching between medications.…”

“…Six studies found that older women (>65/75 years) were less likely to be adherent. 9 , 30 – 33 , 59 However, two studies found the opposite effect 28 , 60 and six studies found no effects. Four studies found that being black was associated with lower odds of adherence than being white, 8 , 31 , 32 , 52 but a further three studies found no significant effects for this relationship.…”

Understanding tamoxifen adherence in women with breast cancer: A qualitative study

“…Studies show that by the fifth year of treatment, up to 50% of women have discontinued (Hadji et al ., ; Owusu et al ., ). Adherence rates range over the course of treatment from 41 to 88% (Murphy, Bartholomew, Carpentier, Bluethmann, & Vernon, ) and fall to 50% by the fifth year of treatment (Lee et al ., ; Partridge, ). As non‐adherence and non‐persistence have similar effects on clinical outcomes, they will both be referred to as ‘(non)‐adherence’ when discussing the implication of the research.…”

“Winging It”: How Older Breast Cancer Survivors Persist With Aromatase Inhibitor Treatment

“…[8][9][10] Limited evidence suggests early discontinuation of hormonal treatments is associated with older age 11,12 and adverse effects 13,14 and usually occurs within the first year, but may also occur in subsequent years. 15,16 However, underlying reasons for these decisions remain poorly understood. 13,17 Because AIs are oral medications that are self-administered in the home setting and started during the transitional survivorship period, 18,19 we wanted to understand what factors are associated with persistence and how these medications fit into the broader life context of older breast cancer survivors from the perspectives of the women themselves.…”