Patient-reported outcomes and early discontinuation in aromatase inhibitor-treated postmenopausal women with early stage breast cancer

Kunal C. Kadakia, Claire F. Snyder, Kelley M. Kidwell, Nicholas J. Seewald, David A. Flockhart, Todd Skaar, Zeruesenay Desta, James M. Rae, Julie Otte, Janet Carpenter, Anna Maria Storniolo, Daniel F. Hayes, Vered Stearns, Norah Lynn Henry

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background. Early discontinuation of aromatase inhibitors (AIs) is common and leads to poor outcomes but is challenging to predict. In the Exemestane and Letrozole Pharmacogenetics trial, a high rate of early discontinuation due to intolerance was observed. We hypothesized that early changes in patient-reported outcomes (PROs) predict AI discontinuation and that biochemical factors are associated with changes in PROs. Patients and Methods. Postmenopausal women with early stage breast cancer enrolled in a prospective randomized trial of exemestane versus letrozole completed questionnaires at baseline and serially over 24months to assess overall quality of life (EuroQOL Visual Analog Scale [VAS]); mood; and multiple symptoms, including a musculoskeletal symptom cluster. A joint mixed-effects/survival model was used to estimate the effect of the change in PROson AI discontinuation. Associations between biochemical factors and change in PROs were examined. Results. A total of 490 patients were analyzed. Worsening of EuroQOL VAS and the musculoskeletal cluster were associated with the highest risk for early discontinuation (hazard ratio [HR], 2.77 [95%confidence interval (CI), 2.72–2.81; p5.015];HR, 4.39 [95% CI, 2.40–8.02; p,.0001], respectively). Pharmacokinetics and estrogen metabolism were not consistently associated with change in PRO measures. No clinically significant differences in any PRO between AIs were observed. Conclusion. Changes in PROs early during AI therapy were associated with treatment discontinuation. Identification of these changes could be used to target interventions in patients at high risk for early discontinuation.

Original languageEnglish (US)
Pages (from-to)539-546
Number of pages8
JournalOncologist
Volume21
Issue number5
DOIs
StatePublished - Mar 23 2016

Fingerprint

Aromatase Inhibitors
exemestane
letrozole
Breast Neoplasms
Visual Analog Scale
Confidence Intervals
Pharmacogenetics
Patient Reported Outcome Measures
Estrogens
Pharmacokinetics
Joints
Quality of Life
Survival
Therapeutics

Keywords

  • Aromatase inhibitors
  • Early discontinuation
  • Patient-reported outcomes
  • Quality of life

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Patient-reported outcomes and early discontinuation in aromatase inhibitor-treated postmenopausal women with early stage breast cancer. / Kadakia, Kunal C.; Snyder, Claire F.; Kidwell, Kelley M.; Seewald, Nicholas J.; Flockhart, David A.; Skaar, Todd; Desta, Zeruesenay; Rae, James M.; Otte, Julie; Carpenter, Janet; Storniolo, Anna Maria; Hayes, Daniel F.; Stearns, Vered; Lynn Henry, Norah.

In: Oncologist, Vol. 21, No. 5, 23.03.2016, p. 539-546.

Research output: Contribution to journalArticle

Kadakia, Kunal C. ; Snyder, Claire F. ; Kidwell, Kelley M. ; Seewald, Nicholas J. ; Flockhart, David A. ; Skaar, Todd ; Desta, Zeruesenay ; Rae, James M. ; Otte, Julie ; Carpenter, Janet ; Storniolo, Anna Maria ; Hayes, Daniel F. ; Stearns, Vered ; Lynn Henry, Norah. / Patient-reported outcomes and early discontinuation in aromatase inhibitor-treated postmenopausal women with early stage breast cancer. In: Oncologist. 2016 ; Vol. 21, No. 5. pp. 539-546.
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T1 - Patient-reported outcomes and early discontinuation in aromatase inhibitor-treated postmenopausal women with early stage breast cancer

AU - Kadakia, Kunal C.

AU - Snyder, Claire F.

AU - Kidwell, Kelley M.

AU - Seewald, Nicholas J.

AU - Flockhart, David A.

AU - Skaar, Todd

AU - Desta, Zeruesenay

AU - Rae, James M.

AU - Otte, Julie

AU - Carpenter, Janet

AU - Storniolo, Anna Maria

AU - Hayes, Daniel F.

AU - Stearns, Vered

AU - Lynn Henry, Norah

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N2 - Background. Early discontinuation of aromatase inhibitors (AIs) is common and leads to poor outcomes but is challenging to predict. In the Exemestane and Letrozole Pharmacogenetics trial, a high rate of early discontinuation due to intolerance was observed. We hypothesized that early changes in patient-reported outcomes (PROs) predict AI discontinuation and that biochemical factors are associated with changes in PROs. Patients and Methods. Postmenopausal women with early stage breast cancer enrolled in a prospective randomized trial of exemestane versus letrozole completed questionnaires at baseline and serially over 24months to assess overall quality of life (EuroQOL Visual Analog Scale [VAS]); mood; and multiple symptoms, including a musculoskeletal symptom cluster. A joint mixed-effects/survival model was used to estimate the effect of the change in PROson AI discontinuation. Associations between biochemical factors and change in PROs were examined. Results. A total of 490 patients were analyzed. Worsening of EuroQOL VAS and the musculoskeletal cluster were associated with the highest risk for early discontinuation (hazard ratio [HR], 2.77 [95%confidence interval (CI), 2.72–2.81; p5.015];HR, 4.39 [95% CI, 2.40–8.02; p,.0001], respectively). Pharmacokinetics and estrogen metabolism were not consistently associated with change in PRO measures. No clinically significant differences in any PRO between AIs were observed. Conclusion. Changes in PROs early during AI therapy were associated with treatment discontinuation. Identification of these changes could be used to target interventions in patients at high risk for early discontinuation.

AB - Background. Early discontinuation of aromatase inhibitors (AIs) is common and leads to poor outcomes but is challenging to predict. In the Exemestane and Letrozole Pharmacogenetics trial, a high rate of early discontinuation due to intolerance was observed. We hypothesized that early changes in patient-reported outcomes (PROs) predict AI discontinuation and that biochemical factors are associated with changes in PROs. Patients and Methods. Postmenopausal women with early stage breast cancer enrolled in a prospective randomized trial of exemestane versus letrozole completed questionnaires at baseline and serially over 24months to assess overall quality of life (EuroQOL Visual Analog Scale [VAS]); mood; and multiple symptoms, including a musculoskeletal symptom cluster. A joint mixed-effects/survival model was used to estimate the effect of the change in PROson AI discontinuation. Associations between biochemical factors and change in PROs were examined. Results. A total of 490 patients were analyzed. Worsening of EuroQOL VAS and the musculoskeletal cluster were associated with the highest risk for early discontinuation (hazard ratio [HR], 2.77 [95%confidence interval (CI), 2.72–2.81; p5.015];HR, 4.39 [95% CI, 2.40–8.02; p,.0001], respectively). Pharmacokinetics and estrogen metabolism were not consistently associated with change in PRO measures. No clinically significant differences in any PRO between AIs were observed. Conclusion. Changes in PROs early during AI therapy were associated with treatment discontinuation. Identification of these changes could be used to target interventions in patients at high risk for early discontinuation.

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KW - Patient-reported outcomes

KW - Quality of life

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