NICE, France—Postmenopausal breast cancer patients given the intravenous bisphosphonate zoledronic acid(Drug information on zoledronic acid) (Zometa) twice a year at the start of adjuvant therapy with the aromatase inhibitor letrozole(Drug information on letrozole) (Femara) had significantly increased bone mineral density (BMD) at 12 months, compared with a delayed-therapy group. Nigel Bundred, MD, of University Hospital, South Manchester, UK, presented the findings at the 5th European Breast Cancer Conference (EBBC) (abstract 12).

The ZO-FAST trial (Zometa-Femara Adjuvant Synergy Trial) randomized 1,065 postmenopausal women with stage I-IIIa, ER- and/or PR-positive breast cancer to receive zoledronic acid, 4 mg as a 15-minute infusion every 6 months beginning on day 1 or delayed until researchers detected a post-baseline BMD T-score greater than 2 SD below normal or after a bone complication occurred.

At 12-month follow-up, patients given zoledronic acid up front had a mean increase in lumbar spine BMD of 2.2% vs a decrease of 3.4% in the delayed group, representing a 5% relative difference (P < .0001). Total hip BMD was also significantly higher in the upfront group (3.5% relative difference, P < .0001). In addition, bone markers were significantly decreased in the upfront patients, compared with the delayed group.

The agent was generally well tolerated; arthralgia was the most common adverse event, occurring in 32.3% of the upfront group and 29.3% of the delayed group.

"We are close to defining the best strategy for addressing the issue of bone loss in women with early breast cancer who receive adjuvant treatment," Dr. Bundred said. "The positive results seen in this trial, which confirm what was observed in other bone loss trials, demonstrate the role of zoledronic acid in prevention and treatment of cancer-treatment-associated bone loss."

AZURE Trial

Novartis, maker of Zometa and Femara, has announced completion of enrollment in AZURE (Does Adjuvant Zoledronic Acid Reduce Recurrence in Patients With High-Risk Localized Breast Cancer?). Researchers believe that inhibition of bone resorption could have an effect on the development and progression of metastatic bone disease. The randomized, open-label, multicenter, parallel-group trial includes 3,360 women with high-risk early breast cancer assigned to receive 4 mg of zoledronic acid plus chemotherapy and/or hormonal therapy or chemotherapy and/or hormonal therapy alone. The primary endpoint is disease-free survival. Secondary endpoints include time to bone metastases, time to distant metastases, overall survival, and reduction of skeletal-related events.