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ZO-FAST: Immediate Zoledronic Acid Beats Delayed Tx in Early Breast Cancer



Major Finding: Immediate treatment with zoledronic acid reduced recurrence and mortality risk by 34% and 31%, respectively, and improved bone density, compared with women assigned to delayed treatment with the bisphosphonate.

Data Source: The multicenter, multinational Z0-FAST (Zometa-Femara Adjuvant Synergy Trial) of 1,065 postmenopausal women with hormone receptor–positive early breast cancer initiating adjuvant endocrine therapy with letrozole with immediate or delayed zoledronic acid therapy at 5 years.

Disclosures: Dr. de Boer is on the speakers’ bureau for Novartis. Dr. Ingle said he had no financial conflicts to disclose.

SAN ANTONIO – Immediate treatment with zoledronic acid in postmenopausal women with hormone receptor–positive breast cancer initiating letrozole therapy was associated with a 34% reduction in recurrence risk and 31% improvement in overall survival, compared with women of similar status who received the bisphosphonate later, according to new data from the ZO-FAST trial.

This study assessed the impact of zoledronic acid (Zometa) on aromatase inhibitor-associated bone loss after surgery for early breast cancer.

Additional disease-free and overall survival benefits were observed among the subgroup of patients who had been postmenopausal for at least 5 years, Dr. Richard de Boer reported yesterday at the San Antonio Breast Cancer Symposium.

The findings update those previously reported by Dr. de Boer of the Royal Melbourne Hospital and colleagues in the ZO-FAST (Zometa-Femara Adjuvant Synergy Trial), demonstrating that early zoledronic acid significantly improved bone mineral density and improved breast cancer disease-free survival.

The new, long-term data confirm the overall survival benefits, and the results of an exploratory subgroup analysis based on menopausal status indicates that the addition of zoledronic acid confers the most benefit to women who are truly menopausal at diagnosis, Dr. de Boer reported.

The study involved 1,065 postmenopausal women with hormone receptor–positive early breast cancer with a bone mineral density T-score of –2. In addition to receiving adjuvant endocrine therapy with 2.5 mg of letrozole (Femara) four times daily for 5 years, the women were randomized to receive 4 mg of zoledronic acid every 6 months either immediately or when their post-baseline T score dipped below –2 or they suffered a nontraumatic/asymptomatic fracture. Patients were included in the analysis if they had established menopause at the time of diagnosis or if they became menopausal as a consequence of chemotherapy or ovarian suppression, Dr. de Boer explained.

At 60 months follow-up, the hazard ratios for recurrence and mortality in the immediate treatment group were 0.66 and 0.69 respectively, with only the former representing a statistically significant improvement over the delayed treatment patients, Dr. de Boer reported. Exploratory analyses of the 670 women who were postmenopausal for more than 5 years or older than 60 years at study entry showed that immediate zoledronic acid treatment significantly improved disease-free survival, with a hazard ratio of 0.63, and significantly prolonged overall survival, with a hazard ratio of 0.50, compared with the delayed treatment group.

With respect to lumbar spine bone mineral density, "the benefits observed in the immediate therapy group early on, when bone loss is at it greatest, continued out over 5 years, with a net difference of 10% favoring the immediate zoledronic acid group," Dr. de Boer said, noting that similar results were observed in total hip bone mineral density, "with an overall change of close to 6% in the immediate group at the 5-year time point."

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