Zometa(R) Enhances Impact of Chemotherapy

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New Data Shows Zometa® Enhances Impact of Chemotherapy on Reducing Breast Tumour Size

FRIMLEY, England, December 11 /PRNewswire/ --

- Adding Zometa to Chemotherapy Prior to Surgery Led to an Additional 33% Reduction in Tumour Size, Resulting in Fewer Mastectomies

- New Data is First to Demonstrate Direct Effect of Zometa to Help Shrink Primary Tumours; Further Evidence of Zometa as a Potential Anticancer Therapy

New data released today demonstrates that the addition of Zometa® (zoledronic acid) infusion to standard chemotherapy before breast cancer surgery reduces the size of breast tumours more effectively than chemotherapy alone in women with early-stage disease.

These neo-adjuvant subset results from the retrospective exploratory analysis of the international AZURE (Adjuvant Zoledronic acid to redUce REcurrence) trial are the first to show the direct effect of Zometa in combination with chemotherapy to help shrink breast tumours, potentially resulting in less radical surgery for some women. These data were presented at the 31st Annual CTRC-AACR San Antonio Breast Cancer Symposium.

"These results support a potential anti-tumour benefit of combining Zometa with chemotherapy in the neoadjuvant treatment of breast cancer," said Matthew Winter, Clinical Research Fellow, University of Sheffield, UK, a lead investigator of this subset analysis. "Adding Zometa to chemotherapy prior to surgery increased tumour shrinkage in this analysis. When breast cancer treatment is given prior to surgery, the goal is to reduce the size of the tumour and in doing so potentially improve breast conservation rates and longer-term outcomes."

In the analysis, pre- and postmenopausal women who received Zometa in addition to chemotherapy before surgery (neo-adjuvant use) experienced a 33% reduction in the size of their primary tumour compared with patients who received chemotherapy alone (14.1 mm reduction in tumour size, P=0.002)(1). The proportion of patients requiring mastectomy was higher (77.9%) in the chemotherapy-alone group than in the Zometa group (65.3%)(2).

"Clinical evidence continues to demonstrate that Zometa may play a role in protecting patients from the return and spread of early-stage breast cancer," said David Epstein, President and CEO, Novartis Oncology. "We are encouraged by these latest results, which show Zometa may help some women avoid having mastectomies, and we remain committed to further exploring the benefit of Zometa as an anticancer treatment."

Zometa is a treatment to reduce or delay bone complications in patients with advanced cancer that has spread to the bones across a broad range of solid tumours, including breast cancer.

The potential anticancer properties of Zometa were previously observed in premenopausal women with early-stage breast cancer from the Austrian Breast & Colorectal Cancer Study Group-12 (ABCSG-12) study, which was presented at the American Society of Clinical Oncology annual meeting (ASCO) earlier this year. Final results from the AZURE trial are expected in the next two to three years.

Novartis is further exploring the anticancer effect of Zometa in a broad clinical program in breast, lung and prostate cancers with the results expected over the next two to three years. Laboratory research has suggested that Zometa may help protect patients with early-stage breast cancer from the return or spread of the cancer to other parts of the body (distant metastatic sites) through several different pathways, including 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).

Study details

AZURE is a randomised, open-label, multicentre, parallel group trial with a five-year treatment phase and a subsequent five-year follow-up phase designed to determine whether Zometa added to standard therapy (chemotherapy and/or hormonal therapy) before (neo-adjuvant) or after (adjuvant) surgery, is superior to each therapy alone in improving disease-free survival in pre- and postmenopausal women with early-stage breast cancer. The trial includes 3,360 patients from 174 centres in seven countries and is coordinated by the Clinical Trials Research Unit (CTRU), University of Leeds, supported by a research grant from Novartis(2).

The neo-adjuvant subset in the current analysis includes 205 participants who received either chemotherapy alone or in combination with Zometa once every three to four weeks for six months prior to breast cancer surgery. Following adjustment for other prognostic factors, the adjusted mean tumour size after treatment was 28.2 millimetres in the Zometa group and 42.4 millimetres in the chemotherapy group, a significant reduction of 33%(1). The pathologic complete response rate (no evidence of residual cancer in the breast or lymph nodes) increased to 10.9% in the Zometa group from 5.8% in the chemotherapy group (P=0.033). The proportion of women needing a mastectomy was reduced by 16% in patients taking Zometa (65.3% in the Zometa group versus 77.9% in the chemotherapy group)(2).

About Zometa

Zometa is indicated for the treatment or prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypocalcaemia) 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 hypocalcaemia 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 SMPC for full Prescribing Information.

About Novartis

Novartis AG provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2007, the Group's continuing operations (excluding divestments in 2007) achieved net sales of USD 38.1 billion and net income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 97,000 full-time associates and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.

References

1 Winter, M.C., et al. AZURE Neoadjuvant ZOL Tumor Reduction presentation. Presented at CIBD and SABCS 2008.

2 Winter, M.C., et al. The Addition of Zoledronic Acid to Neoadjuvant Chemotherapy May Influence Pathological Response - Exploratory Evidence for Direct Anti-tumor Activity in Breast Cancer. SABCS, 2008 Abstract.

3. Gnant, M. et al. Adjuvant Endocrine Therapy Plus Zoledronic Acid in Premenopausal Women With Early Breast Cancer: First Efficacy Results from ABCSG-12. The New England Journal of Medicine, 2008

Distributed by PR Newswire on behalf of Novartis Pharmaceuticals UK Ltd

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