[Abstract] Associations between treatment-emergent symptoms and early discontinuation of aromatase inhibitor (AI) therapy

Abstract

Background: The Exemestane and Letrozole Pharmacogenetics (ELPh) trial addressed associations between pharmacogenetics and effects of AI therapy. Here we describe changes in health-related quality-of-life (HRQOL) measures during AI therapy. We hypothesized that negative effects of AI therapy on HRQOL predict for early discontinuation.

Methods: Postmenopausal women initiating AI therapy were enrolled on the ELPh trial and randomized to exemestane or letrozole for 24 months (mo). Patients completed questionnaires at baseline (BL) and serially over 24 mo, including the EuroQOL Visual analogue scale (VAS) (range 0-100), Centers for Epidemiologic Studies Depression Scale (CESD) (range 0-60), Anxiety subscale of Hospital Anxiety and Depression Scale (HADSA) (range 0-21), and a symptom assessment analyzed as 6 symptom clusters (SC): body image, vasomotor, vulvovaginal, musculoskeletal (MSK), cognitive, mood (range 0-4). A joint mixed effects and survival model was used to estimate the effect of the change in HRQOL scores over 24 mo on AI discontinuation. All HRQOL measures were treated as continuous variables.

Results: 490 patients were analyzed with no significant differences between BL HRQOL measures by drug. 155 (32%) patients discontinued AI therapy within 24 mo. Each 1-point decrease in EuroQOL VAS was significantly associated with an increased risk of early discontinuation (hazard ratio (HR), 2.77; 95% confidence interval (CI) 2.72-2.81, p = 0.015). Changes in CESD and HADSA were also associated with early discontinuation (HR 1.04; 95% CI 1.01-1.06, p = 0.001 and HR 1.08; 95% CI 1.02-1.14, p = 0.006, respectively). Each 1-point increase in the MSK (HR 4.39; 95% CI 2.40-8.02, p < 0.0001), cognitive (HR 3.45; 95% CI 2.07-5.74, p < 0.0001), mood (HR 2.50; 95% CI 1.42-4.41, p = 0.002), and body image (HR 2.12; 95% CI 1.10-4.08, p = 0.025) SC were associated with early discontinuation.

Conclusions: In this hypothesis-generating analysis, worsening of multiple treatment-related symptoms during AI therapy predicted early discontinuation of AI. If confirmed in independent trials, serial changes in HRQOL could be utilized to target interventions in patients at high-risk for early discontinuation. Clinical trial information: NCT00228956.

Nicholas J. Seewald

Assistant Professor of Biostatistics

Assistant Professor of Biostatistics at the University of Pennsyvlania Perelman School of Medicine