Predictors of Aromatase Inhibitor Discontinuation as a Result of Treatment-Emergent Symptoms in Early-Stage Breast Cancer

Abstract

Purpose Aromatase inhibitors (AIs) are effective for treatment of hormone receptor–positive breast cancer, but adherence and persistence with therapy are poor. Predictors of treatment discontinuation are not clearly defined. It is unknown whether patients with intolerable toxicity from one AI are able to tolerate another. Patients and Methods Women with early-stage breast cancer initiating AI therapy were enrolled onto a multicenter, prospective, open-label randomized trial of exemestane versus letrozole. Patients completed symptom questionnaires at baseline and serially during therapy. Patients who developed AI-associated intolerable symptoms and discontinued treatment were given the option to switch to the other study AI after a 2- to 8-week washout period. Results Of the 503 enrolled women, 32.4% discontinued initial AI therapy within 2 years because of adverse effects; 24.3% discontinued specifically because of musculoskeletal symptoms. Median time to treatment discontinuation as a result of any symptom was 6.1 months (range, 0.1 to 21.2 months) and was significantly shorter in patients randomly assigned to exemestane (hazard ratio [HR], 1.5; 95% CI, 1.1 to 2.1; P = .02). Younger age and taxane-based chemotherapy were associated with higher likelihood of treatment discontinuation (HR, 1.4; 95% CI, 1.02 to 1.9; P = .04; and HR, 1.9; 95% CI, 1.00 to 3.6; P = .048, respectively). Of the 83 patients who chose to switch to the second AI, 38.6% continued the alternate AI for a median of 13.7 months. Conclusion Premature discontinuation of initial AI therapy as a result of symptoms is common, although more than one third of patients may be able to tolerate a different AI medication. Additional research is needed to identify predictive tools and interventions for AI-associated treatment-emergent symptoms.

Management of aromatase inhibitor induced musculoskeletal symptoms in postmenopausal early Breast cancer: A systematic review and meta-analysis

“…Analysis of longitudinal claims data from three American commercial health programs revealed sub-optimal adherence to anastrozole in 19-28% of patients in their first year of treatment (14). These statistics are consistent with other studies of aromatase inhibitor adherence (15)(16)(17)(18), which report a significant percentage of patients displaying early discontinuation of treatment. There are important clinical implications of this data, as non-compliance with adjuvant endocrine therapies in early breast cancer has been shown to be detrimental to the patients' survival (16).…”

Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity

“…Furthermore, the number of toxicities that increased in PM and IM patients was exceeded by the number that decreased, including significant improvements in the FACT breast cancer subscale and trial outcome index in IM patients. These improvements in quality of life could be partially attributable to decreased adherence, particularly in patients with toxicity [31], or may be a consequence of remaining on treatment for an extended period of time. It is possible that over time patients learn to prevent, manage, or accept side effects associated with tamoxifen treatment; however, there was no association between time on tamoxifen treatment before enrollment and any of the composite toxicity measures at baseline (data not shown).…”

Adherence to Endocrine Therapy in Breast Cancer Adjuvant and Prevention Settings

“…A randomized adjuvant adherence trial found shorter time to treatment discontinuation for exemestane, compared with letrozole (HR, 1.5; 95% CI, 1.1-2.1; ref. 27).…”