Researchers affiliated with the Austrian Breast & Colorectal Cancer Study Group Trial 12 (ABCSG-21) have reported that the addition of adjuvant Zometa® (zoledronic acid) to endocrine therapy for the treatment of hormone-positive, early breast cancer significantly improved progression-free and recurrence-free survival beyond the effects of endocrine therapy alone among premenopausal women. These results were recently presented as a late-breaking abstract at the 2008 annual American Society for Clinical Oncology (ASCO) meeting in Chicago, Illinois May 30 to June 2.

The bisphosphonate Zometa is approved for the treatment of hypercalcemia of malignancy, as well as the treatment of documented bone metastases from solid tumors or multiple myeloma, in conjunction with antineoplastic therapy. Research has indicated that Zometa may have properties that lend to direct antineoplastic effects, an issue that is being explored in studies at present. Researchers also continue to evaluate Zometa in early stages of various types of cancer to assess its effectiveness in the prevention of bone metastasis and other outcome endpoints, with over 20,000 patients in 10 different countries enrolled in Zometa trials at present.

The current study, the Austrian Breast & Colorectal Cancer Study Group Trial 12 (ABCSG-21), was a multicenter, open-label Phase III study that included 1,803 premenopausal women with Stages I-II, hormone-positive breast cancer. Patients had fewer than 10 involved axillary lymph nodes. Following curative surgery and initiation of the gonadotropin-releasing hormone analog goserelin for ovarian suppression, patients were enrolled and randomized into one of four treatment groups: 1) Arimidex® (anastrozole) plus Zometa; 2) Arimidex alone; 3) Nolvadex® (tamoxifen) plus Zometa; 4) Nolvadex alone. Treatment was continued for three years; the median follow-up of the trial was five years. Disease-free survival in all treatment groups was the primary endpoint; recurrence-free survival, overall survival and safety were secondary endpoints. Bone-metastases-free survival was an exploratory endpoint of the trial.

• Compared with hormone therapy alone, the addition of Zometa improved disease-free survival by 36% (p=0.01) and recurrence-free survival by 35% (p=0.015).
• Patients treated with Zometa had a survival of 98% compared with 94% for the control group (p=0.10).
• Patients treated with Zometa had a trend toward a lower risk of developing bone metastases (p>0.05).
• Longer follow-up and a larger number of events are necessary to truly determine significance of overall survival and the risk of the development of bone metastases.
• There were no reported cases of osteonecrosis of the jaw (ONJ); side effects were consistent with the known drug safety profile.

These researchers stated: “There is in fact an indication that zoledronic acid exerts its benefit through a variety of mechanisms, altogether obviously creating a tumor-hostile environment that helps kill micrometastases.” Dr. Gnant, the lead investigator of the study also hinted that these results may provide a clearer picture into providing a standard of care for this group of patients that may not include chemotherapy. Further studies with the inclusion of chemotherapy as a comparator are warranted.

Comments: These are among the first data to suggest that there is a specific anti-tumor effect of bisphosphonates.

Related News:

Early Zometa® Prevents Bone Loss in Postmenopausal Women with Breast Cancer Receiving Femara® (3/4/2008)

Zometa® Prevents Bone Loss in Pre and Postmenopausal Breast Cancer Patients (12/19/2007)

Zometa® Prevents Bone Loss in Premenopausal Breast Cancer Patients (1/17/2007)

Intravenous Zometa® Improves Bone Mineral Bone Density in Postmenopausal Women (2/28/2002)

Reference: Gnant, M. et al. Efficacy of Zoledronic acid in premenopausal women with breast cancer receiving adjuvant endocrine therapy - the ABCSG-12 trial. Presented at: the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill., 31 May - 2 June, 2008; Abstract LBA4.