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Final 5‐year results of Z‐FAST trial
Author(s) -
Brufsky Adam M.,
Harker W. Graydon,
Beck J. Thaddeus,
Bosserman Linda,
Vogel Charles,
Seidler Christopher,
Jin Lixian,
Warsi Ghulam,
ArgonzaAviles Eliza,
Hohneker John,
Ericson Solveig G.,
Perez Edith A.
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26313
Subject(s) - medicine , zoledronic acid , bone mineral , clinical endpoint , letrozole , osteoporosis , urology , breast cancer , surgery , bone resorption , bone remodeling , randomized controlled trial , cancer , aromatase
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. Cancer 2012. © 2011 American Cancer Society.