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    Major Independent Trial Demonstrates Significant Anticancer Benefit Of Zometa(R) In Premenopausal Women With Early-Stage Breast
    By Anna Ohlden | May 31st 2008 09:32 AM | Print | E-mail | Track Comments

    FRIMLEY, England, May 31 /PRNewswire/ --

    - 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 (1)

    - Findings may Allow Clinicians to Improve Standard of Care for Premenopausal Women Diagnosed With Hormone-Sensitive, Early-Stage Breast Cancer

    - These are the First Data From a Large Clinical Programme Exploring the Direct Anticancer Effect of Zometa in Breast, Lung and Prostate Cancer

    New data presented today showed that Zometa(R) (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.

    "There remains a significant unmet medical need to improve cancer- related clinical outcomes in premenopausal women with early stage, hormone-sensitive breast cancer, who are naturally very concerned about the possible return of their cancer", said Professor Rob Coleman, Honorary Consultant Medical Oncologist at the Cancer Research Centre, Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield. "The significant reduction in the risk of recurrence demonstrated by these findings, through the addition of a simple well tolerated six monthly 15 minute infusion of zoledronic acid, suggests a new standard of care for this group of women."

    According to Cancer Research UK, each year approximately 12,000 women die from breast cancer in the UK each year.(2) Moreover, the incidence of breast cancer in the UK has risen by 12% in the last ten years.(2)

    Carolyn Rogers, Clinical Nurse Specialist at Breast Cancer Care, said: " We know that many premenopausal women who have been treated for early stage, hormone-sensitive breast cancer live with the anxiety of their cancer returning.

    "The initial findings of this study are encouraging and indicate that in addition to its current uses, zoledronic acid may provide anti-tumour benefits and could reduce the risk of breast cancer returning. We look forward to the results of further trials currently underway examining these properties of zoledronic acid. Longer term follow up should be carried out to fully determine the benefit to patients.

    "Women should be reassured that current approved treatment options are very successful."

    Approximately one-third of women with hormone-sensitive, early breast cancer experience a recurrence with the majority appearing in other organs and tissues. These distant recurrences, or metastases, are the primary cause of death from breast cancer, with 60% of women dying within five 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%, compared to hormone therapy alone. Furthermore, the risk of recurrence-free survival events fell by 35% 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 tumours. 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.

    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 tumour passes through six stages on its path to metastasising (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 tumour cell apoptosis (programmed cell death) and increasing the activity of anticancer agents that target tumour cell metastases(3).

    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.

    References

    (1) 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.

    (2) Cancer Research UK (last visited 27/05/08). http://info.cancerresearchuk.org/cancerstats/types/breast/

    (3) Mundy, GR, et al. Metastases to bone: causes, consequences and therapeutic opportunities. Nature Reviews Cancer. 2002;2:584-593.

    Notes to editors

    Study details

    The Austrian Breast & Colorectal Cancer Study Group Trial 12 (ABCSG-12) is an open-label, multicentre, Phase III study that enrolled 1,803 premenopausal women with oestrogen-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 1 mg/d plus Zometa 4 mg q6m; (2) anastrozole 1 mg/d alone; (3) tamoxifen 20 mg/d plus Zometa 4 mg q6m; (4) tamoxifen 20 mg/d 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).

    About Zometa

    Zometa is indicated for the treatment of prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in patients with advanced malignancies involving bone. Zometa is approved and indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumours, in conjunction with standard antineoplastic therapy. An intravenous bisphosphonate, Zometa is the only therapy to demonstrate efficacy in reducing or delaying bone complications across a broad range of tumour types such as breast, prostate, lung and renal cell cancers in patients with metastatic disease when administered monthly. Zometa offers patients, nurses and clinicians a convenient 4 mg, 15-minute infusion.

    Important safety information

    In clinical studies, the safety profile with Zometa was similar to that of pamidronate. Zometa has been associated with reports of renal insufficiency. Patients should have serum creatinine assessed prior to receiving each dose of Zometa. Caution is advised when Zometa is used in aspirin-sensitive patients, or with aminoglycosides, loop diuretics, and other potentially nephrotoxic drugs. Due to the risk of clinically significant deterioration in renal function, single doses of Zometa should not exceed 4 mg and the duration of infusion should be no less than 15 minutes in 100 ml of diluent.

    In clinical trials in patients with bone metastases and hypercalcaemia of malignancy (HCM), Zometa had a safety profile similar to other intravenous bisphosphonates. The most commonly reported adverse events included flu-like syndrome (fever, arthralgias, myalgias, skeletal pain), fatigue, gastrointestinal reactions, anaemia, weakness, cough, dyspnoea and oedema. Zometa should not be used during pregnancy. Zometa is contraindicated in patients with clinically significant hypersensitivity to zoledronic acid or other bisphosphonates, or any of the excipients in the formulation of Zometa.

    Osteonecrosis of the Jaw (ONJ): ONJ has been reported in patients with cancer receiving treatment including bisphosphonates, chemotherapy, and/or corticosteroids. The majority of reported cases have been associated with dental procedures such as tooth extraction. A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors. While on treatment, these patients should avoid invasive dental procedures if possible. No data are available to suggest whether discontinuation of bisphosphonate therapy reduces the risk of ONJ in patients requiring dental procedures.

    Please see full Prescribing Information.

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    For more information, please contact: Fiona Turner, Novartis Pharmaceuticals UK Ltd, Tel: +44(0)1276-698086, Fax: +44(0)1276-698605, Email: fiona.turner@novartis.com; Charlotte Binstead, Red Health, Tel: +44(0)207-025-6592, Fax: +44(0)207-025-6499, Email: charlotte.binstead@redconsultancy.com