Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors

Kunal C. Kadakia, Kelley M. Kidwell, Nicholas J. Seewald, Claire F. Snyder, Anna Maria Storniolo, Julie L. Otte, David A. Flockhart, Daniel F. Hayes, Vered Stearns, N. Lynn Henry

Research output: Contribution to journalArticle

Abstract

Purpose: Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression. Methods: Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole. Those that discontinued for intolerance were offered protocol-directed crossover to the other AI after a washout period. Changes in PROs, including pain [Visual Analog Scale (VAS)] and functional status [Health Assessment Questionnaire (HAQ)], were compared after 3 months on the first versus the second AI. Estradiol and drug concentrations were measured. Results: Eighty-three patients participated in the crossover protocol, of whom 91.3% reported improvement in symptoms prior to starting the second AI. Functional status worsened less after 3 months with the second AI (HAQ mean change AI #1: 0.2 [SD 0.41] vs. AI #2: −0.05 [SD 0.36]; p = 0.001); change in pain scores was similar between the first and second AI (VAS mean change AI #1: 0.8 [SD 2.7] vs. AI #2: −0.2 [SD 2.8]; p = 0.19). No statistical differences in estradiol or drug concentrations were found between those that continued or discontinued AI after crossover. Conclusions: Although all AIs act via the same mechanism, a subset of patients intolerant to one AI report improved PROs with a different one. The mechanism of this tolerance remains unknown, but does not appear to be due to non-adherence to, or insufficient estrogen suppression by, the second AI.

Original languageEnglish (US)
Pages (from-to)411-419
Number of pages9
JournalBreast Cancer Research and Treatment
Volume164
Issue number2
DOIs
StatePublished - Jul 1 2017

Keywords

  • Aromatase inhibitors
  • Arthralgia
  • Crossover
  • Patient outcome assessment
  • Quality of life

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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