Fax: (412) 641-2296
Final 5-year results of Z-FAST trial†
Adjuvant Zoledronic Acid Maintains Bone Mass in Postmenopausal Breast Cancer Patients Receiving Letrozole
Article first published online: 10 OCT 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 5, pages 1192–1201, 1 March 2012
How to Cite
Brufsky, A. M., Harker, W. G., Beck, J. T., Bosserman, L., Vogel, C., Seidler, C., Jin, L., Warsi, G., Argonza-Aviles, E., Hohneker, J., Ericson, S. G. and Perez, E. A. (2012), Final 5-year results of Z-FAST trial. Cancer, 118: 1192–1201. doi: 10.1002/cncr.26313
Study results were presented in part at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009 (Abstract 4083).
- Issue published online: 17 FEB 2012
- Article first published online: 10 OCT 2011
- Manuscript Accepted: 2 MAY 2011
- Manuscript Revised: 11 APR 2011
- Manuscript Received: 19 JAN 2011
- zoledronic acid;
- aromatase inhibitors;
- breast neoplasm;
- bone resorption
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.
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.
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.
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. Cancer 2012. © 2011 American Cancer Society.