Adjuvant Zoledronic Acid Decreases Breast Ca Recurrence in Premenopausal Women

May 31, 2008

Adding zoledronic acid to anastrozole or tamoxifen therapy decreased recurrence by 35% and increased disease free survival by 36% in premenopausal breast cancer patients, according to results of the Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12). The multicenter, Phase III trial is the first large trial to demonstrate the significant antitumor benefit of zoledronic acid, said Michael Gnant, MD, Medical University of Vienna. "Adjuvant treatment with zoledronic acid should be considered in order to improve the standard of care in premenopausal breast cancer patients," he said.

Adding zoledronic acid to anastrozole or tamoxifen therapy decreased recurrence by 35% and increased disease free survival by 36% in premenopausal breast cancer patients, according to results of the Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12). The multicenter, Phase III trial is the first large trial to demonstrate the significant antitumor benefit of zoledronic acid, said Michael Gnant, MD, Medical University of Vienna. "Adjuvant treatment with zoledronic acid should be considered in order to improve the standard of care in premenopausal breast cancer patients," he said.

ABCSG-12 included 1803 women with estrogen-receptor-positive stage I or II breast cancer and involvement of fewer than 10 lymph nodes. All had undergone curative surgery and initiation of ovarian suppression with goserelin 3.6 mg every 28 days. Study patients had no or only neoadjuvant chemotherapy. They were randomized to receive either anastrozole 1 mg/day or tamoxifen 20 mg/day alone, anastrozole plus zoledronic acid 4 mg every 6 months, or tamoxifen plus zoledronic acid for 3 years.

The median follow up was 5 years. The primary endpoint was disease-free survival (local recurrence, contralateral breast cancer, distant metastasis, secondary carcinoma and/or death from any cause). Secondary endpoints were recurrence-free survival, defined as the length of time after randomization without an event, overall survival, and safety.

There were 137 disease-free survival events and 42 deaths. Overall survival was 98.2% and the 5-year disease-free survival rate was 94%. Researchers found no significant differences between the two groups receiving hormone therapy alone. However, the addition of zoledronic acid reduced the number of disease-free survival events by 36% (p = 0.01) and the risk of recurrence-free survival events by 35% (p = 0.015). There were non-significant trends toward reduced bone metastases and risk of death among patients receiving zoledronic acid.

The combination of endocrine therapy and zoledronic acid was well tolerated. There were no serious zoledronic acid-related adverse events, no renal toxicity, and no cases of jaw osteonecrosis. Side effects were as expected with bisphosphonate treatment. Dr. Gnant said these results suggest that low- and intermediate-risk patient subgroups with endocrine-responsive breast cancer can be spared the side effects of cytotoxic therapy after locoregional treatment.

Another trial is underway to evaluate whether zoledronic acid reduces the risk of cancer recurrence in patients with Stage II and III breast cancer. The Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) study has enrolled 3,360 patients and includes both premenopausal and postmenopausal women.