Zoledronic Acid Improves Bone Loss Associated With Adjuvant AI Therapy in Postmenopausal BC Patients

[Janette]

By Jennifer Reising

SAN ANTONIO, Tex -- December 15, 2009 -- The bone mineral density (BMD) of postmenopausal women with early breast cancer receiving adjuvant letrozole who received upfront zoledronic acid progressively increased from baseline to 5 years, compared with those who received delayed zoledronic acid.

Five-year follow-up results of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST) were presented here on December 12 at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS).

"The final results of the study show that upfront zoledronic acid is increasingly more effective than delayed zoledronic acid in preventing bone loss associated with adjuvant aromatase-inhibitor [AI] therapy at 5 years, compared with at 12 months after the start of treatment," said Adam Brufsky, MD, Magee-Womens Hospital, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. "Zoledronic acid was also found to be safe and well tolerated through 5 years."

The Z-FAST study evaluated the efficacy and safety of zoledronic acid in preventing AI-associated bone loss in postmenopausal women with early breast cancer who received adjuvant letrozole. The primary endpoint was the percent change in lumbar spine (LS) BMD at 12 months (previously reported).

The original study involved 602 postmenopausal women with stage I to IIIa oestrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive breast cancer starting letrozole 2.5 mg/day for 5 years. Patients were then randomised in a 1:1 ratio to receive upfront intravenous zoledronic acid 4 mg every 6 months or delayed zoledronic acid.

There were 355 patients who completed the follow-up 5-year study, with 180 patients who received upfront zoledronic acid and 175 patients who received delayed zoledronic acid.

Long-term results showed that the benefit of upfront zoledronic acid increased at 5 years versus 1 year. At 12 months, LS BMD was 4.4% higher in the upfront group than in the delayed group (P < .0001), and total hip (TH) BMD was 3.3% higher (P < .0001).

In contrast, at 5 years of follow-up, LS BMD was 8.6% higher (P < .001) in the upfront zoledronic acid group, with a mean increase of 6.2%, compared with the delayed arm, which showed a mean decrease of 2.4%. The TH BMD was 6.7% higher (P < .001) in the upfront zoledronic acid, with a mean increase of 2.6%, while the delayed arm showed a mean decrease of 4.1%.

No patients in the upfront zoledronic acid group became severely osteopenic, compared with 4.9% of patients in the delayed group. In addition, 17.7% of patients in the delayed group met criteria that required the initiation of zoledronic acid.

Funding for this study was provided by Novartis Pharmaceuticals Corporation.