Final 5-year results of Z-FAST trial: Adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole

Adam M. Brufsky, W. Graydon Harker, J. Thaddeus Beck, Linda Bosserman, Charles Vogel, Christopher Seidler, Lixian Jin, Ghulam Warsi, Eliza Argonza-Aviles, John Hohneker, Solveig G. Ericson, Edith A. Perez

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Background: Postmenopausal breast cancer (BC) patients receiving adjuvant aromatase inhibitor therapy are at risk of progressive bone loss and fractures. Zoledronic acid inhibits osteoclastic bone resorption, is effective in maintaining bone health, and may therefore be beneficial in this setting. Methods: Overall, 602 postmenopausal women with early, hormone receptor-positive BC receiving adjuvant letrozole were randomized (301 each group) to receive upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months) for 5 years. The primary endpoint was the change in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary endpoints included changes in LS BMD, total hip BMD, and bone turnover markers at 2, 3, and 5 years; fracture incidence at 3 years; and time to disease recurrence. Results: At month 61, the adjusted mean difference in LS and total hip BMDs between the upfront and delayed groups was 8.9% and 6.7%, respectively (P <.0001, for both). Approximately 25% of delayed patients received zoledronic acid by month 61. Only 1 patient experienced grade 4 renal dysfunction; no confirmed cases of osteonecrosis of the jaw were reported. Fracture rates (upfront, 28 [9.3%]; delayed, 33 [11%]; P =.3803) and Kaplan-Meier disease recurrence rates (upfront, 9.8 [95% confidence interval (CI), 6.0-10.3]; delayed, 10.5 [95% CI, 6.6-14.4]; P =.6283) were similar at month 61. Conclusions: Upfront zoledronic acid seems to be the preferred treatment strategy versus delayed administration, as it significantly and progressively increases BMD in postmenopausal women with early BC receiving letrozole for 5 years, and long-term coadministration of letrozole and zoledronic acid is well tolerated.

Original languageEnglish (US)
Pages (from-to)1192-1201
Number of pages10
JournalCancer
Volume118
Issue number5
DOIs
StatePublished - Mar 1 2012

Fingerprint

letrozole
zoledronic acid
Bone Density
Breast Neoplasms
Bone and Bones
Spine
Pelvic Bones
Confidence Intervals
Recurrence
Aromatase Inhibitors
Osteonecrosis
Bone Remodeling
Bone Fractures
Bone Resorption
Jaw
Hip
Hormones
Kidney

Keywords

  • aromatase inhibitors
  • bone resorption
  • breast neoplasm
  • postmenopause
  • zoledronic acid

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Brufsky, A. M., Harker, W. G., Beck, J. T., Bosserman, L., Vogel, C., Seidler, C., ... Perez, E. A. (2012). Final 5-year results of Z-FAST trial: Adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole. Cancer, 118(5), 1192-1201. https://doi.org/10.1002/cncr.26313

Final 5-year results of Z-FAST trial : Adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole. / Brufsky, Adam M.; Harker, W. Graydon; Beck, J. Thaddeus; Bosserman, Linda; Vogel, Charles; Seidler, Christopher; Jin, Lixian; Warsi, Ghulam; Argonza-Aviles, Eliza; Hohneker, John; Ericson, Solveig G.; Perez, Edith A.

In: Cancer, Vol. 118, No. 5, 01.03.2012, p. 1192-1201.

Research output: Contribution to journalArticle

Brufsky, AM, Harker, WG, Beck, JT, Bosserman, L, Vogel, C, Seidler, C, Jin, L, Warsi, G, Argonza-Aviles, E, Hohneker, J, Ericson, SG & Perez, EA 2012, 'Final 5-year results of Z-FAST trial: Adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole', Cancer, vol. 118, no. 5, pp. 1192-1201. https://doi.org/10.1002/cncr.26313
Brufsky, Adam M. ; Harker, W. Graydon ; Beck, J. Thaddeus ; Bosserman, Linda ; Vogel, Charles ; Seidler, Christopher ; Jin, Lixian ; Warsi, Ghulam ; Argonza-Aviles, Eliza ; Hohneker, John ; Ericson, Solveig G. ; Perez, Edith A. / Final 5-year results of Z-FAST trial : Adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole. In: Cancer. 2012 ; Vol. 118, No. 5. pp. 1192-1201.
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abstract = "Background: Postmenopausal breast cancer (BC) patients receiving adjuvant aromatase inhibitor therapy are at risk of progressive bone loss and fractures. Zoledronic acid inhibits osteoclastic bone resorption, is effective in maintaining bone health, and may therefore be beneficial in this setting. Methods: Overall, 602 postmenopausal women with early, hormone receptor-positive BC receiving adjuvant letrozole were randomized (301 each group) to receive upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months) for 5 years. The primary endpoint was the change in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary endpoints included changes in LS BMD, total hip BMD, and bone turnover markers at 2, 3, and 5 years; fracture incidence at 3 years; and time to disease recurrence. Results: At month 61, the adjusted mean difference in LS and total hip BMDs between the upfront and delayed groups was 8.9{\%} and 6.7{\%}, respectively (P <.0001, for both). Approximately 25{\%} of delayed patients received zoledronic acid by month 61. Only 1 patient experienced grade 4 renal dysfunction; no confirmed cases of osteonecrosis of the jaw were reported. Fracture rates (upfront, 28 [9.3{\%}]; delayed, 33 [11{\%}]; P =.3803) and Kaplan-Meier disease recurrence rates (upfront, 9.8 [95{\%} confidence interval (CI), 6.0-10.3]; delayed, 10.5 [95{\%} CI, 6.6-14.4]; P =.6283) were similar at month 61. Conclusions: Upfront zoledronic acid seems to be the preferred treatment strategy versus delayed administration, as it significantly and progressively increases BMD in postmenopausal women with early BC receiving letrozole for 5 years, and long-term coadministration of letrozole and zoledronic acid is well tolerated.",
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AU - Vogel, Charles

AU - Seidler, Christopher

AU - Jin, Lixian

AU - Warsi, Ghulam

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