Post-tamoxifen Use Of Femara In Postmenopausal Women With Early Breast Cancer Reduced Risk Of Recurrence By Nearly Half (43%) and Significantly Improved Disease-Free Survival, According to Data Presented at Major Medical Meeting

Extended adjuvant data presented at San Antonio Breast Cancer Symposium supported by new data on quality of life with Femara vs. placebo, from same clinical trial

East Hanover, NJ, December 5, 2003 - Extended adjuvant treatment with Femara (letrozole tablets) in a group of postmenopausal women with early breast cancer who had completed five years of therapy with tamoxifen cut the risk of recurrence of early breast cancer nearly in half (43%), and newly analyzed data showed the quality of life for patients on Femara was generally comparable to that of patients taking placebo, according to data presented today at the San Antonio Breast Cancer Symposium. This independent, international study was coordinated by the National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario.

"Femara is the first therapy shown to reduce the risk of recurrence in postmenopausal breast cancer patients after five years of tamoxifen," said Diane Young, MD, vice president, global head, clinical development, Novartis Oncology. "These new data are encouraging because they suggest that in addition to the potential benefit of reduced risk of recurrence, Femara was seen to be well-tolerated and the safety profile was consistent with previous clinical trials without unduly compromising patient's quality of life."

Quality of life included patients' ability to engage in activities of everyday living, including work and recreation, subjective evaluation of mood and emotion and occurrence of adverse events as measured by the SF-36 Health Survey, a general health status questionnaire. SF-36 has been widely used both in well and chronic disease populations and is recognized to be reliable and valid. A Menopause-Specific Quality of Life Questionnaire also was included in the quality of life assessment.

Study Highlights
The international breast cancer trial of nearly 5,200 women, called MA-17, is the first study designed to examine the effectiveness of an aromatase inhibitor, Femara, in the extended adjuvant setting, which is the period following five years of post-surgery tamoxifen treatment. During this period, women do not typically receive drug therapy despite the ongoing risk of breast cancer recurrence.

At a median follow-up of 2.4 years, the data in the Femara group showed a 43% reduction in risk of overall recurrence compared with placebo (P=0.00008) as well as a significant reduction (46%) in contralateral disease (cancer occurring in the other breast). The estimated absolute improvement in disease free survival at four years was 6% for postmenopausal patients taking Femara compared with placebo (93% Femara vs. 87% placebo). These numbers are nearly twice those the investigators anticipated when they designed the trial. The study was originally designed to show a 2.5% improvement in four-year disease free survival, from a baseline of 88% in the placebo arm. Disease free survival is defined as the time from randomization to the time of first recurrence of the primary disease in the breast (including contralateral breast), chest wall, nodal or metastatic sites.

According to data from the Early Breast Cancer Trialists' Group, Oxford, UK, more than 50% of breast cancer recurrence happens in women later than five years after diagnosis. Tamoxifen, which reduces the risk of breast cancer recurrence during the first five years of post-surgical therapy, has been shown not to be beneficial beyond five years of treatment. Approximately one million postmenopausal women worldwide currently receive tamoxifen therapy for reduction of breast cancer recurrence.

Study Details
The MA-17 study is a Phase III, global, double-blind, randomized, multi-center trial. The primary objective of the study is to compare the disease free survival of postmenopausal women taking Femara vs. placebo after approximately five years of tamoxifen therapy. Ninety-eight percent of the participants have known receptor positive tumors. The remaining patients have tumors that are estrogen receptor unknown. Women were randomized to the two arms of the study and, prior to the change in protocol, were to have received five years of daily treatment with either 2.5 mg of Femara or placebo by mouth. Those who switch from placebo to the Femara arm of the study now will be eligible to receive treatment with Femara.

Secondary objectives of the MA-17 study include comparison of overall survival, incidence of contralateral breast cancer, long-term safety of Femara and quality of life. In addition, subsets of the study are exploring the effect of Femara on lipid metabolism and bone mineral density. According to the interim analysis, no difference in cholesterol levels have been seen between study arms, nor have there been any differences in patient-reported cardiovascular events to date.

The international study is being coordinated by the National Cancer Institute of Canada Clinical Trials Group in Kingston, Ontario. The interim data were published earlier this year in the November 6 issue of The New England Journal of Medicine.

Additional Femara Adjuvant Clinical Trial
A second Phase III adjuvant study with Femara is being conducted by the Breast International Group (BIG 1-98) in collaboration with Novartis. This study has four treatment arms comparing five years of Femara, five years of tamoxifen, two years of Femara followed by three of tamoxifen, and two years of tamoxifen followed by three years of Femara. Recruitment in the BIG 1-98 trial was recently closed, with more than 8,000 women enrolled.

About Femara
Femara, a leading, once-a-day oral aromatase inhibitor, is indicated for first-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer. Femara is also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.

Femara Contraindications and Adverse Events
In the MA-17 analysis, the most common adverse events were hot flashes, sweating, edema, hypercholesterolemia, headache, arthalgia, myalgia, fatigue, constipation and dizziness, in greater than 10% of patients in either arm of the study. Of these, hot flashes, arthralgia, and myalgia were more common in those receiving Femara than placebo (P<0.05). Vaginal bleeding was more common in those taking placebo (P<0.05).

The number of women reporting a new bone fracture to date is 77/2166 (3.6%) in the Femara group, compared with 63/2157 (2.9%) in the placebo group (P=0.24). The authors noted a trend to more newly diagnosed osteoporosis in women taking Femara (124/2166 [5.7%]) vs. placebo (97/2157 [4.5%]) (P=0.07).

Femara is generally well tolerated and is contraindicated in patients with known hypersensitivity to Femara or any of its excipients. The most commonly reported adverse events for Femara vs. tamoxifen were bone pain (22% vs. 21%), hot flashes (19% vs. 16%), back pain (18% vs. 19%), nausea (17% vs. 17%), dyspnea or labored breathing (18% vs. 17%), arthralgia (16% vs. 15%), fatigue (13% vs. 13%), coughing (13% vs. 13%), constipation (10% vs. 11%), chest pain (6% vs. 6%) and headache (8% vs. 6%). Femara may cause fetal harm when administered to pregnant women. There is no clinical experience to date on the use of Femara in combination with other anticancer agents. The incidence of peripheral thromboembolic events, cardiovascular events, and cerebrovascular events was 3-4% in each treatment arm.

The foregoing release contains forward-looking statements that can be identified by terminology such as "significant progress," "consistently demonstrated remarkable results," "compelling," "improved," "benefited significantly," "recommend," "may have substantial impact," "look forward to data," "help answer the question," or similar expressions, or by express or implied discussions regarding potential new indications for Femara or potential future sales of Femara, or regarding the long-term impact of a patient's use of Femara. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Femara to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Femara will be approved for any additional indications in any market. Nor can there be any guarantee regarding potential future sales of Femara. Neither can there be any guarantee regarding the long-term impact of a patient's use of Femara. In particular, management's expectations regarding commercialization of Femara could be affected by, among other things, additional analysis of Femara clinical data; new clinical data; unexpected clinical trial results; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; increased government pricing pressures; and other risks and factors referred to in the Company's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected.

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