The effect of zoledronic acid on aromatase inhibitor associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36 months follow-up of ZO-FAST.

Abstract

Abstract Abstract #44 Background: Aromatase inhibitors (AI) administered alone or sequentially following tamoxifen are the preferred treatments for hormone-receptor-positive (HRP) early breast cancer (EBC) in postmenopausal women (PMW). As a class effect, long term AI use is associated with an increased loss of bone loss. The primary analysis at 12 months of the Z-FAST and ZO-FAST studies demonstrated that the loss of bone mineral density (BMD) can effectively be prevented by zoledronic acid (ZA). Also, the ABCSG-12 study recently demonstrated a positive impact by ZA on disease recurrence in pre-menopausal women. This 36-months (mo) follow-up for ZO-FAST provides an insight into these issues and longer term safety data as pre-planned secondary endpoints.
 Materials and Methods: ZO-FAST has 1064 PMW with HRP EBC receiving Let (2.5 mg qd x 5 yrs). Pts with a BMD T-score >-2 were randomized to immediate ZA arm (IMZA) vs delayed ZA arm (DZA). DZA pts receive ZA when either the post baseline T-score decreases to < -2.0 or if a non-traumatic fracture occurs. All patients underwent a spine x-ray at baseline and at 36-mo to assess for asymptomatic fractures.
 Results: The updated primary endpoint continues to demonstrate the benefit of IMZA vs. DZA, with a treatment difference of 9.29(p<0.0001) at the lumbar spine and 5.41(p<0.0001) at the hip. 110 pts (20.5%) in the DZA have started ZA as per protocol at a median of 11.8 mo (range 0.03-38.3). The majority of these (82 pts) for T-score < –2.0. There were 24(4.6%) pts who experienced clinical fractures in the IMZA and 26(4.9%) in DZA (Fisher's exact test:p value=0.88). A total of 676 pts (335 IMZA and 341 DZA) had both baseline and 36-mo spine x-ray reviewed centrally. The log rank test for disease recurrence (22 events-IMZA vs 37-DZA) has a p value of 0.0423. The log rank test for disease free survival (26 vs 43) has a p value of 0.0336. The median duration of Let is 43.3 vs 43.4 mo. Adverse events remain as previously reported, and are consistent with the known safety profile of the study drugs.
 Conclusion: The 36-month data continues to demonstrate the efficacy of ZA in preventing BMD loss. The trends in disease events are significant though preliminary at this 36 month analysis. Further follow up is needed to confirm these promising results. These benefits are observed in the context of a favorable safety profile. To date in this relatively small sample size, the rates of fracture are low and similar. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 44.