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 journalArticle

1 Citation (Scopus)

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)1-9
Number of pages9
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - May 11 2018
Externally publishedYes

Fingerprint

zoledronic acid
letrozole
Aromatase Inhibitors
exemestane
Pharmacogenetics
Diphosphonates
Bone Density
Linear Models
Incidence

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A phase II study evaluating the efficacy of zoledronic acid in prevention of aromatase inhibitor-associated musculoskeletal symptoms : the ZAP trial. / Santa-Maria, Cesar A.; Bardia, Aditya; Blackford, Amanda L.; Snyder, Claire; Connolly, Roisin M.; Fetting, John H.; Hayes, Daniel F.; Jeter, Stacie C.; Miller, Robert S.; Nguyen, Anne; Quinlan, Katie; Rosner, Gary L.; Slater, Shannon; Storniolo, Anna Maria; Wolff, Antonio C.; Zorzi, Jane; Henry, Nora Lynn; Stearns, Vered.

In: Breast Cancer Research and Treatment, 11.05.2018, p. 1-9.

Research output: Contribution to journalArticle

Santa-Maria, CA, Bardia, A, Blackford, AL, Snyder, C, Connolly, RM, Fetting, JH, Hayes, DF, Jeter, SC, Miller, RS, Nguyen, A, Quinlan, K, Rosner, GL, Slater, S, Storniolo, AM, Wolff, AC, Zorzi, J, Henry, NL & Stearns, V 2018, 'A phase II study evaluating the efficacy of zoledronic acid in prevention of aromatase inhibitor-associated musculoskeletal symptoms: the ZAP trial', Breast Cancer Research and Treatment, pp. 1-9. https://doi.org/10.1007/s10549-018-4811-1
Santa-Maria, Cesar A. ; Bardia, Aditya ; Blackford, Amanda L. ; Snyder, Claire ; Connolly, Roisin M. ; Fetting, John H. ; Hayes, Daniel F. ; Jeter, Stacie C. ; Miller, Robert S. ; Nguyen, Anne ; Quinlan, Katie ; Rosner, Gary L. ; Slater, Shannon ; Storniolo, Anna Maria ; Wolff, Antonio C. ; Zorzi, Jane ; Henry, Nora Lynn ; Stearns, Vered. / A phase II study evaluating the efficacy of zoledronic acid in prevention of aromatase inhibitor-associated musculoskeletal symptoms : the ZAP trial. In: Breast Cancer Research and Treatment. 2018 ; pp. 1-9.
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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.",
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T1 - A phase II study evaluating the efficacy of zoledronic acid in prevention of aromatase inhibitor-associated musculoskeletal symptoms

T2 - the ZAP trial

AU - Santa-Maria, Cesar A.

AU - Bardia, Aditya

AU - Blackford, Amanda L.

AU - Snyder, Claire

AU - Connolly, Roisin M.

AU - Fetting, John H.

AU - Hayes, Daniel F.

AU - Jeter, Stacie C.

AU - Miller, Robert S.

AU - Nguyen, Anne

AU - Quinlan, Katie

AU - Rosner, Gary L.

AU - Slater, Shannon

AU - Storniolo, Anna Maria

AU - Wolff, Antonio C.

AU - Zorzi, Jane

AU - Henry, Nora Lynn

AU - Stearns, Vered

PY - 2018/5/11

Y1 - 2018/5/11

N2 - 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.

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KW - Arthralgias

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KW - Quality of life

KW - Survivorship care

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