Coleman, Ann Oncol 2013 - Zoledronic Acid (Zoledronate) for Postmenopausal Women with Early Breast Cancer Receiving Adjuvant Letrozole (ZO-FAST Study): Final 60-Month Results - Article Summary

Zoledronic Acid (Zoledronate) for Postmenopausal Women with Early Breast Cancer Receiving Adjuvant Letrozole (ZO-FAST Study): Final 60-Month Results

Coleman, Bundred, et al.·Ann Oncol·2013·339 citations·RCT

Background

Aromatase inhibitors are the preferred adjuvant endocrine therapy for the majority of postmenopausal women with hormone-responsive early breast cancer. Although generally more effective than tamoxifen, aromatase inhibitor therapy is associated with increased bone loss and fracture risk.

Methods

Postmenopausal women receiving adjuvant letrozole (2.5 mg/day for 5 years; N = 1065) were randomly assigned to immediate zoledronic acid (zoledronate) 4 mg every 6 months for 5 years, or delayed zoledronate (initiated for fracture or on-study bone mineral density [BMD] decrease).
The primary end point was the change in lumbar spine BMD at 12 months.
Lumbar spine and total hip BMD at subsequent follow-up, disease-free survival (DFS), and overall survival were assessed as secondary end points.

Results

At 60 months (final analysis), the mean change in lumbar spine BMD was +4.3% with immediate zoledronate and −5.4% with delayed intervention (P < 0.0001).
Immediate zoledronate reduced the risk of DFS events by 34% (hazard ratio [HR] = 0.66; P = 0.0375) with fewer local (0.9% versus 2.3%) and distant (5.5% versus 7.7%) recurrences versus delayed zoledronate.
In the delayed group, delayed initiation of zoledronate substantially improved DFS versus no zoledronate (HR = 0.46; P = 0.0334).

Conclusions

Immediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS compared with letrozole alone.

Supplemental

Zoledronic Acid (Zoledronate) for Postmenopausal Women with Early Breast Cancer Receiving Adjuvant Letrozole (ZO-FAST Study): Final 60-Month Results