Three Trials Affirm Anticancer Benefit of Zometa in Early-Stage Breast Cancer

By Matthew Mahady
Published: Monday, May 24, 2010


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New data from 3 clinical trials indicate that Zometa (zoledronic acid), manufactured by Novartis, reduces the risk of local and distant breast cancer recurrence in pre- and postmenopausal women with early stage disease (stage I or II). Investigators presented results of the studies in Stockholm, Sweden, at the 33rd Annual ESMO Congress.

The trials included ABCSG (Austrian Breast and Colorectal Cancer Study Group)-12, a phase III study that evaluated the addition of Zometa to endocrine therapy; Z-FAST/ZO-FAST, a phase III study that measured Zometa’s effect on aromatase inhibitor (AI)–associated bone loss in postmenopausal women with early stage breast cancer who took letrozole (Femara) after resection; and an ongoing pilot study that is tracking 45 patients who have undergone various presurgical and postsurgical therapies. A joint press release said the findings add to a growing body of research that suggest Zometa helps protect patients against the return or spread of early stage breast cancer.

The ABCSG-12 trial was an open label multicenter study that enrolled 1803 premenopausal women who had hormone-responsive early stage breast cancer. Patients were randomized to receive adjuvant endocrine therapy with goserelin acetate (Zoladex) in combination with anastrozole (Arimidex) or tamoxifen (Nolvadex/Istubal/Valodex) alone or in combination with Zometa. The women underwent treatment for 3 years and were followed up on for a median of 2 years after treatment ended. Researchers found that Zometa significantly prolonged disease-free survival (DFS) and recurrence-free survival (RFS) and reduced the risk of DFS events by 33% (P = .02) and RFS events by 32% (P = .03)

compared with endocrine therapy alone.

The Z-FAST/ZO-FAST trial examined the effect of Zometa on AI-associated bone loss in 1667 postmenopausal women with early breast cancer who received letrozole after surgery. Participants were randomized to receive therapy with Zometa either up front or only after researchers detected bone loss. Findings support the conclusion that Zometa contributes to a reduction in the risk of recurrence. A 24-month integrated analysis of the trial found that 3.6% of women who received Zometa before the apparent onset of bone loss experienced disease recurrence (defined as local recurrence, distant metastasis, or death) compared with 5.5% of women who received Zometa only after showing symptoms of bone loss. In a stratified analysis, administering Zometa up front significantly decreased the risk of DFS events, by 43% (P = .0183).

Data from the third clinical trial, a pilot study involving 45 women with early stage breast cancer, suggest that Zometa therapy decreases the prevalence of disseminated tumor cells in bone marrow. In women with early stage breast cancer, the presence of these cells in the bone marrow is associated with distant recurrence and death. At 2-year follow-up, a decrease in disseminated cancer cells was seen in 12 of the 17 patients evaluated (71%; P = .01). The study is ongoing, and additional data are necessary to assess whether the results become statistically significant.

“The evidence for the anticancer effect of zoledronic acid is building,” said Hugh O’Dowd, head of Novartis’ Business Oncology Unit in the United Kingdom. “These data further suggest that zoledronic acid significantly reduces the risk of breast cancer recurrence in this patient population and may represent a new treatment option.”

Approximately one-third of women who receive a diagnosis of hormone-sensitive breast cancer in its early stages will experience a recurrence after treatment. The majority of these recurrences are metastatic, appearing in other organs and tissues. These distant metastatic recurrences are associated with a 5-year mortality rate of 60% and constitute the primary cause of death in women with breast cancer.

A growing number of upcoming clinical studies plan to examine the potential anticancer effects of Zometa. One of the largest of these studies, AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence), has just finished enrolling 3360 premenopausal and postmenopausal women with stage II or III breast cancer. AZURE will evaluate the impact of Zometa in reducing the risk of cancer recurrence in these women.






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