Clinical Newswire December 12, 2009 (San Antonio USA)-
Zoledronic acid prevents bone loss in post-menopausal women receiving letrozole as adjuvant therapy for breast cancer, according to the final results of the Z-FAST trial presented at the 32nd annual San Antonio Breast Cancer Symposium.*
Bone loss and potential fracture are a known complication of breast cancer therapy with aromatase inhibitors (AIs). The Z-FAST trial tested the hypothesis that intermittent zoledronic acid might prevent bone loss in postmenopausal women treated with AIs. The 5-year final Z-FAST results were presented in a poster by Adam Brufsky, MD, PhD of the University of Pittsburgh Medical Center, confirming the previously reported preliminary results.
The trial investigators randomized 602 postmenopausal women with ER+ and/or PR+ early breast cancer to receive letrozole (2.5 mg/day) with either upfront zoledronic acid (4 mg IV every 6 months) (N=301) or delayed zoledronic acid (4 mg IV every 6 months) (N=301). The primary endpoint was the percent change in lumbar spine (LS) bone mineral density at 12 months. The secondary endpoints were: percent change in LS bone mineral density at months 24, 36, and 61; percent change in total hip (TH) bone mineral density and changes in markers of bone turnover at 12, 24, 36, and 61 months; incidence of clinical fractures at 36 months; time to disease progression; and rate of decrease in LS and TH bone mineral density from baseline to month 61.
By the 61 month visit, 74 (24.7%) of the delayed zoledronic acid patients had initiated zoledronic acid therapy. At 61 months, the mean percent change in LS bone mineral density from baseline was 6.19% in the upfront zoledronic acid group versus 2.42% in the delayed zoledronic acid group (p<0.0001 INTERGROUP comparisons; p≦0.0003 intragroup comparisons from baseline). The mean percent change in TH bone mineral density from baseline was 2.57% in the upfront zoledronic acid group versus -4.12% in the delayed zoledronic acid group (p<0.001 INTERGROUP comparisons; p≦0.0001 intragroup comparisons from baseline).
There were fewer clinical fractures in the upfront zoledronic acid group (9.3%) compared with the delayed zoledronic acid group (11.0%). The rate of disease recurrence or death at 61 months was lower in the upfront group (7.6%) compared with the delayed group (8.3%). However, the study was not statistically designed to measure a significant difference between the upfront and delayed zoledronic acid groups with respect to clinical fractures or disease recurrence.
The safety results showed that renal insufficiency was infrequent and generally manageable when it occurred. There were no confirmed cases of osteonecrosis of the jaw, study drug related atrial fibrillation, or serious study drug related infections.
Dr. Brufsky concluded that zoledronic acid prevents bone loss in the hip and spine in postmenopausal women treated with letrozole as adjuvant breast cancer therapy. Zoledronic acid showed a favorable risk to benefit profile for the prevention of bone loss in women receiving adjuvant AI therapy in this trial. The benefits of zoledronic acid in the adjuvant setting may extend beyond bone mineral density improvement to prevention of disease recurrence. This hypothesis is currently being tested in the AZURE trial.
*Brufsky A, Harker WG, Beck JT, et al. The effect of zoledronic acid on aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: The Z-FAST study 5-year final follow-up. SABCS2009. Abstract 4083.
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