Zoledronic acid effectively inhibits cancer treatment-induced bone loss in postmenopausal women with early breast cancer receiving adjuvant Letrozole: 12 mos BMD results of the Z-FAST trial

Aromatase inhibitors are effective therapies for postmenopausal women with breast cancer. Their use has been associated with increased bone resorption markers and bone loss at the lumbar spine/total hip.

This multicenter open-label randomized study evaluates the efficacy and safety of Zoledronic acid in preventing cancer treatment induced bone loss in postmenopausal women with early breast cancer who are receiving aromatase inhibitor therapy. The study involved 602 postmenopausal women with stage I-IIIa ER+ and/or PR+ breast cancer starting Letrozole (2.5 mg qd x 5 yrs) were randomized to upfront zoledronic acid (4 mg IV infusion q 6 mos) vs delayed zoledronic acid in 93 centers in the US and Canada. The delayed group will receive zoledronic acid when either post-baseline T-score decreases <-2 SD or in case of fracture. The primary endpoint is the percent change in lumbar spine BMD at 12 mos. The researchers found that baseline characteristics were similar between groups. 343 of 602 pts (170 upfront/173 delayed) are evaluable for 12 mos lumbar spine BMD. Upfront zoledronic acid group shows a mean increase of 2.02% while the delayed group shows a mean decrease of 2.61%, resulting in a significant difference of 4.63% between groups (p<0.001). 347 of 602 pts (175 upfront/172 delayed) are evaluable for 12 mos total hip BMD. Upfront zoledronic acid group shows a mean increase of 1.40% while the delayed group shows a mean decrease of 2.10%, resulting in a significant difference of 3.50% between groups (p<0.001). Serum markers of bone turnover (N-Telopeptide, Bone-Specific Alkaline Phosphatase) were collected and analyzed on a subset of 226 pts at 3 month intervals for 1 yr. The results showed significant suppression of both markers over 12 mos in favor of upfront vs delayed zoledronic acid group. Zoledronic acid was safe and well tolerated. Updated 12 mos BMD data on all pts will be presented at the meeting. Researchers concluded that upfront zoledronic acid prevents cancer treatment-induced bone loss in postmenopausal women with early breast cancer receiving adjuvant Let at 12 mos. Zoledronic acid in combination with Let in this setting offers the potential to combine the anti-cancer efficacy of Let with the bone protective effect of zoledronic acid.(Source: American Society of Clinical Oncology June 2005 conference: Abstract 533.)