Zometa, an osteoporosis drug from Novartis, failed to improve disease free survival of early breast cancer patients in a substantial clinical trial, the results of which were presented today at the 2010 San Antonio Breast Cancer Symposium.



The AZURE trial included 3360 patients from 174 centres. Prof Robert Coleman, of the University of Sheffield, England, and colleagues randomized stage II and III patients to standard therapy or standard therapy plus zoledronic acid for five years.


The use of Zometa made no difference to survival in the study's overall population though there was some benefit in older patients. There was a 29 percent improvement in overall survival observed in the 1,101 patients who were five years post-menopause.



Further info regarding the AZURE trial:

AZURE is a randomized, open-label, multicenter, parallel group trial that enrolled 3,360 women from 174 centers in seven countries. The study is run by the National Cancer Research Network in the United Kingdom with input from an international collaborative group4. Patients participate in a five-year treatment phase and a subsequent five-year follow-up phase4. A small subset of patients also received neo-adjuvant (pre-surgery) therapy4.
 
The primary endpoint of DFS was to be determined after 940 disease events4. 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 DFS, overall survival, bone metastasis free survival safety, and other translational endpoints. After a median follow up of 59 months (interquartile range 53-61), the hazard ratio (HR) for DFS in Zometa-treated (n=1681) compared to control patients (n=1678) was 0.98 (95% confidence interval [CI] [0.85-1.13], P=0.79), thus there was no clinically significant benefit between the treatment groups. The trend toward improved overall survival in patients on the Zometa arm was not statistically significant (HR=0.85 [95% CI 0.72-1.01], 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 Zometa 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 [95% CI 0.54-0.94]; P=0.017)1. No benefit was seen in premenopausal women.
 
The tolerability profile of Zometa is well-established and results from this study were found to be consistent with the known profile. Generally, serious adverse events (SAE) were similar in both treatment arms. There were 17 cases of osteonecrosis of the jaw confirmed in the Zometa arm. This represents a rate of 1.16%, which is consistent with what has been seen in other well controlled trials.