Major Independent Trial Demonstrates Significant Anticancer Benefit of Zometa(R) in Premenopausal Women With Early-Stage Breast Cancer

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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Source: Novartis Pharmaceuticals UK Ltd

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

2008-05-31 10:19:06 0374121 PRNEWSWIRE