A phase II study evaluating the efficacy of zoledronic acid in prevention of aromatase inhibitor-associated musculoskeletal symptoms: the ZAP trial

Cesar A. Santa-Maria, Aditya Bardia, Amanda L. Blackford, Claire Snyder, Roisin M. Connolly, John H. Fetting, Daniel F. Hayes, Stacie C. Jeter, Robert S. Miller, Anne Nguyen, Katie Quinlan, Gary L. Rosner, Shannon Slater, Anna Maria Storniolo, Antonio C. Wolff, Jane Zorzi, Nora Lynn Henry, Vered Stearns

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Purpose: Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) are common adverse events of AIs often leading to drug discontinuation. We initiated a prospective clinical trial to evaluate whether bisphosphonates are associated with reduced incidence of AIMSS. Methods: In the single-arm trial, the Zoledronic Acid Prophylaxis (ZAP) trial, we compared the incidence of AIMSS against historical controls from the Exemestane and Letrozole Pharmacogenomics (ELPh) trial. Eligible women were postmenopausal with stage 0-III breast cancer planning to receive adjuvant AIs. AIMSS was assessed using the Health Assessment Questionnaire and Visual Analog Scale over 12 months in both trials. Participants in the ZAP trial received zoledronic acid prior to initiating letrozole and after 6 months; ELPh participants included in the analysis were taking letrozole but not bisphosphonates. We analyzed patient-reported outcomes (PROs) and bone density in the ZAP trial using mixed-effects linear regression models and paired t tests, respectively. Results: From 2011 to 2013, 59 postmenopausal women enrolled in ZAP trial. All 59 (100%) women received baseline and 52 (88%) received 6-month zoledronic acid, and had similar characteristics to historical controls from the ELPh trial (n = 206). Cumulatively during the first year of AI, 37 and 67% of ZAP and ELPh participants reported AIMSS (p < 0.001), respectively. Within the ZAP trial, we did not observe significant changes in other PROs; however, we report improvements in bone mineral density. Conclusions: Compared to historical controls, zoledronic acid administered concomitantly with adjuvant AIs was associated with a reduced incidence of AIMSS. A randomized controlled trial is required to confirm these findings.

Original languageEnglish (US)
Pages (from-to)121-129
Number of pages9
JournalBreast Cancer Research and Treatment
Volume171
Issue number1
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

Keywords

  • Aromatase inhibitors
  • Arthralgias
  • Bisphosphonates
  • Quality of life
  • Survivorship care

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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