Results from the second interim analysis of the Phase III AZURE ( Adjuvant Zoledronic acid to redUce Recurrence ) trial have shown that Zoledronic acid ( Zometa ) did not demonstrate a disease-free survival advantage when added to standard adjuvant chemotherapy and/or hormonal therapy in pre- and postmenopausal women with early breast cancer.
In a preplanned analysis based on menopausal status, a benefit in disease free survival and overall survival was seen in women with well-established menopause in the Zoledronic acid arm.

The AZURE trial was conducted to determine if Zometa as adjuvant therapy had a benefit in preventing recurrences in premenopausal and postmenopausal women with early breast cancer.
The results were presented at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium in San Antonio, Texas.

The potential anticancer benefit of Zometa was previously observed in a large, randomized, Phase III study from the Austrian Breast & Colorectal Cancer Study Group ( ABCSG-12 study ), which included more than 1,800 premenopausal women with hormone receptor-positive ( HR+ ) early-stage breast cancer who, following curative surgery and hormone therapy, including Goserelin treatment to suppress ovarian function and induce menopause, were treated with or without Zoledronic acid for three years. The trial showed that the addition of three years of Zoledronic acid therapy to hormonal therapy following surgery improved disease-free survival by 32% ( hazard ratio, HR=0.68, P=0.009 )

AZURE is a randomized, open-label, multicenter, parallel group trial that enrolled 3,360 women from 174 centers in seven countries. Patients participate in a five-year treatment phase and a subsequent five-year follow-up phase. A small subset of patients also received neo-adjuvant therapy.

The primary endpoint of disease-free survival was to be determined after 940 disease events. The data presented at SABCS are from a second interim analysis performed when at least 75% ( 752 ) of the final events had occurred.
Secondary endpoints included invasive disease-free survival, overall survival, bone metastasis free survival, safety, and other translational endpoints. After a median follow up of 59 months, the hazard ratio for disease-free survival in Zoledronic acid-treated ( n=1681 ) compared to control patients ( n=1678 ) was 0.98 ( P=0.79 ), thus there was no clinically significant benefit between the treatment groups. The trend toward improved overall survival in patients on the Zoledronic acid arm was not statistically significant ( HR=0.85, P=0.0726 ).

In a preplanned analysis of women based on menopausal status, a benefit of disease free survival and overall survival was seen in women with well-established menopause in the Zoledronic acid arm. An adjusted analysis for imbalances in prognostic factors ( estrogen receptor, lymph node status and tumor stage ) showed this benefit was statistically significant ( 29% improvement in overall survival; HR=0.71; P=0.017 ). No benefit was seen in premenopausal women.

The tolerability profile of Zoledronic acid is well-established and results from this study were found to be consistent with the known profile. Generally, serious adverse events were similar in both treatment arms. There were 17 cases of osteonecrosis of the jaw confirmed in the Zoledronic arm. This represents a rate of 1.16%, which is consistent with what has been seen in other well controlled trials.

Source: Novartis, 2010

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