The FINANCIAL — New data presented on May 31 showed that Zometa (zoledronic acid) offered a significant anticancer benefit for premenopausal women with hormone-sensitive, early-stage breast cancer.
The study found that Zometa when added to hormone therapy, following surgery, significantly reduced the risk of cancer returning or death by 36% beyond clinical benefits achieved with hormone therapy alone.
"Investigators from the Austrian Breast & Colorectal Cancer Study Group (ABCSG) announced the findings during a plenary presentation today at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois, USA." Novartis reports.
"This study is the first large-scale trial to demonstrate the significant antitumor benefit of zoledronic acid," said lead investigator Michael Gnant, M.D., of the Medical University of Vienna. "These new findings may allow oncologists to further improve the standard of care for premenopausal women with hormone-sensitive breast cancer."
According to the World Health Organization (WHO), each year approximately 500,000 women die worldwide because their breast cancer has returned or spread[2]. Moreover, the incidence of breast cancer has been rising in recent decades[3].
"These results represent a tremendous advance for women hoping to prevent the return of their cancer," said David Epstein, President and CEO of Novartis Oncology. "We continue to explore the anticancer benefit of Zometa in a large clinical program with nearly 20,000 patients in 10 trials worldwide. We anticipate additional results over the next two to three years."
The ABCSG-12 study, in which women were treated for three years and observed for an additional two years, demonstrated that the addition of Zometa to hormone therapy (tamoxifen or anastrozole) significantly prolonged both disease-free survival and recurrence-free survival. With Zometa, the risk of disease-free survival events (which include death from any cause) fell by 36% (P=0.01), compared to hormone therapy alone. Furthermore, the risk of recurrence-free survival events fell by 35% (P=0.015) with Zometa, compared to hormone therapy alone. A positive but non-significant trend toward an overall survival benefit was also seen in patients who received Zometa[1].
Zometa is the world's leading treatment for the prevention or delay of skeletal-related events (SREs) in patients with advanced malignancies involving bone across a broad range of tumors. Laboratory research had suggested that Zometa may also help protect patients from the spread of cancer to other parts of the body (distant metastatic sites) and help keep patients recurrence-free.
Zometa slows the bone-destroying effect that occurs with bone metastases by fighting abnormal activation of osteoclasts, cells that normally break down old bone, and osteoblasts, cells that normally build new bone. Growth factors produced by cancer cells overstimulate osteoclasts and osteoblasts, causing excessive erosion of bone and/or the abnormal buildup of new but unstable bone.
Laboratory research has suggested that Zometa may also have anticancer effects, including helping to protect against the return and spread of cancer before it reaches an advanced stage. A tumor passes through six stages on its path to metastasizing (spreading). In the laboratory, Zometa has been shown to make passage through these stages more difficult by inhibiting angiogenesis (formation of blood vessels that grow and feed cancer cells), stimulating cancer-fighting T-cells, inducing tumor cell apoptosis (programmed cell death) and increasing the activity of anticancer agents that target tumor cell metastases[4].
A growing number of clinical studies are examining the potential anticancer impact of Zometa. One of the largest of these studies, AZURE (Adjuvant Zoledronic acid to redUce REcurrence), has completed enrollment. The study will evaluate the impact of Zometa in reducing risk of cancer recurrence in 3,360 premenopausal and postmenopausal women with Stage II/III breast cancer.
Another study presented at this year's ASCO meeting evaluated the effect of Zometa on bone marrow micrometastases. The study was conducted in 120 premenopausal and postmenopausal women with Stage II/III breast cancer undergoing treatment pre- and post-surgery. For those women who were negative for disseminated cancer cells at baseline, significantly more women who took Zometa in addition to chemotherapy remained negative for disseminated cancer cells over time.
Study details
The Austrian Breast & Colorectal Cancer Study Group Trial 12 (ABCSG-12) is an open-label, multicenter, Phase III study that enrolled 1,803 premenopausal women with estrogen-receptor-positive Stage I or II breast cancer, with fewer than 10 axillary lymph nodes involved. Patients were recruited for the study after curative surgery and initiation of goserelin treatment for ovarian suppression, and randomly assigned into one of four study groups: (1) anastrozole plus Zometa; (2) anastrozole alone; (3) tamoxifen plus Zometa; (4) tamoxifen alone. The treatment period was three years and the median follow-up period was an additional two years[1].
The primary endpoint of the study was disease-free survival for all four study groups. Recurrence-free survival, overall survival, and safety were secondary endpoints. (Disease-free survival was defined as the length of time after randomization during which patients had no local recurrence, contralateral breast cancer, distant metastasis, secondary carcinoma, and/or death from any cause. Recurrence-free survival was defined as the length of time after randomization during which patients had no local recurrence, contralateral breast cancer, distant metastasis, and/or secondary carcinoma.) Exploratory endpoints included bone-metastases-free survival[1].
At the median follow-up of five years, disease-free survival events were reduced by 36% (P=0.01) with Zometa and the risk of recurrence-free survival events fell by 35% (P=0.015) versus hormone therapy alone. Sixteen deaths had occurred among patients who received Zometa with hormone therapy versus 26 deaths in patients who received hormone therapy alone, which resulted in a nonsignificant reduction in the risk of death in patients who received Zometa compared with those who received hormone therapy alone (P=0.103). A similar trend was noted toward a reduction in bone metastases among patients who received Zometa compared with those who received hormone therapy alone (16 versus 23). Longer follow-up and a larger number of events will be necessary to determine if any significant differences exist between the groups for overall survival and bone-metastases-free survival. Overall, treatment was generally well-tolerated and side effects were consistent with known drug safety profile[1].
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