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Data show significant overall benefit in disease free survival across all post- menopausal women with hormone receptor-positive early breast cancer (19 per cent, p=0.003); especially reducing spread to distant sites of the body (27 per cent; p=0.006) |
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Femara® demonstrated a particularly strong advantage in disease free survival vs. tamoxifen in women at greatest risk of recurrence (such as node-positive patients and those with prior chemotherapy) |
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Femara®is now the only treatment shown to significantly reduce risk of recurrence both as initial therapy post-surgery and also following five years of standard tamoxifen treatment |
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Novartis will file for adjuvant use with global regulatory authorities in mid-2005 |
Dorval, Quebec, January 26, 2005 - Adjuvant use of Femara® (letrozole) in postmenopausal women with hormone receptor-positive early breast cancer demonstrated a significant 19 per cent reduction in risk of recurrence (p=0.003), as well as reducing the risk that the cancer would spread to other parts of the body (distant metastases) by 27 per cent, compared with the reductions offered by tamoxifen (p=0.006) according to an independent, international study presented today by the International Breast Cancer Study Group. The data, from the Breast International Group (BIG) 1-98 trial are from a head-to-head comparison of Femara® with tamoxifen in more than 8,000 women treated at a median follow-up of 26 months.
"Femara® has already shown a significant reduction in risk of breast cancer recurrence after five years of tamoxifen therapy in the MA-17 study," said Dr. Kathy Pritchard, medical oncologist at Toronto Sunnybrook Regional Cancer Centre and Women's College Health Sciences Centre. "This data shows Femara® is also beneficial to women in the early adjuvant setting. This is great news for the treatment of breast cancer and Femara®."
The BIG 1-98 trial demonstrated a particularly strong disease free survival advantage for patients at the highest risk of breast cancer recurrence in the adjuvant (post-surgery) setting, such as those with node-positive early breast cancer (cancer that already spread to lymph nodes at the time of diagnosis), and those who have received prior chemotherapy. These women are more likely to develop distant metastases and, therefore, may be at greater risk of dying from their disease.
Disease free survival, the primary efficacy endpoint in this study, was defined as the time from randomization to recurrence (including recurrence restricted to the breast after breast conserving treatment, whichever occurred first), metastasis, appearance of a second primary tumour, or death from any cause.
Study Details
Postmenopausal women with early breast cancer in 27 countries enrolled in this Phase III, randomized, double-blind, controlled clinical trial, supported by Novartis.
There was a statistically significant reduction of 17 per cent in the risk of systemic failure (the time from randomization to systemic recurrence, appearance of a second non breast malignancy, or death without recurrence, whichever occurred first) (p=0.02). There was a 14 per cent reduction in risk of death in favour of Femara® that was not significant. Patients will continue to be monitored to track disease status, survival and long-term tolerability.
These positive data complement those of the landmark MA-17 trial (an international study, led by the National Cancer Institute of Canada Clinical Trials Group at Queen's University in Kingston, Ontario, with funding from the Canadian Cancer Society) for the use of Femara® in the extended adjuvant setting. Femara® is the only aromatase inhibitor shown to be effective in both the adjuvant and extended adjuvant settings. The term extended adjuvant describes the pe-riod following standard adjuvant treatment with tamoxifen. Femara® is approved for extended adjuvant treatment of early breast cancer in 20 countries worldwide, and is currently under re-view by Health Canada.
"This is exciting news for breast cancer patients and Novartis. Femara® is the only hormonal therapy that has been shown to significantly reduce the risk of breast cancer recurrence in postmenopausal women with early breast cancer after standard tamoxifen therapy, known as the extended adjuvant setting. Now we have the first evidence that Femara® also offers a significant disease free survival advantage over tamoxifen in the adjuvant setting in this population," said Diane Young, MD, Vice President and Global Head, Clinical Development, Novartis Oncology.
Preliminary results of this trial show that patients treated with Femara® had significant reduc-tions in vaginal bleeding, hot flushes, and endometrial cancer when compared to tamoxifen. Hypercholesterolemia, grade 3-5 stroke and other cardiovascular events were more common in Femara®. As expected with estrogen deprivation therapy, the number of women reporting new bone fractures to date was 5.8 per cent on Femara® and 4.1 per cent on tamoxifen. Grade 3-5 thromboembolic events were more common in tamoxifen treated patients. Overall, more pa-tients in the study died on tamoxifen than Femara®. However, in patients whose breast cancer did not recur, more deaths due to stroke were reported in Femara® treated patients than ta-moxifen treated patients (7 vs. 1) and cardiac causes (26 vs. 13). These events combined with all deaths from causes other than recurrence of breast cancer were not statistically significant. Fur-ther analysis of these preliminary data is ongoing. In the interim, routine assessments of bone mineral density and cholesterol levels with active treatment when necessary should be consid-ered.
BIG 1-98 is the only clinical trial designed to incorporate both a head-to-head comparison of Femara
® with tamoxifen during the first five years following breast cancer surgery and a sequencing of both agents to determine the most effective approach to minimize the risk of recurrence. Patients were randomized to the following arms: tamoxifen for five years, Femara
® for five years, tamoxifen for two years followed by Femara
® for three years, and Femara
® for two years followed by tamoxifen for three years. Results from the ongoing arms of the study, which are expected to determine which treatment is more effective, monotherapy or sequential therapy, and if sequential therapy, which sequence is more effective, are expected in 2008.
About Femara®
Femara®(letrozole) is a once-a-day oral aromatase inhibitor that is indicated as first-line treat-ment of postmenopausal women with advanced breast cancer.
Femara® is also indicated for the hormonal treatment of advanced/metastatic breast cancer in women with natural or artificially-induced postmenopausal status, who have disease
progression following antiestrogen therapy.
Contraindications, warnings and adverse events
In previous clinical trials, the most common adverse events experienced with Femara® are hot flushes, arthralgia/arthritis and myalgia. Other commonly reported adverse reactions are: nausea, fatigue, anorexia, appetite increase, peripheral oedema, headache, dizziness, vomiting, dyspepsia, constipation, diarrhea, alopecia, increased sweating, rash, myalgia, bone pain, arthri-tis/arthralgia, and weight increase.
Femara® is contraindicated in women who are pregnant or breast-feeding as well as in premeno-pausal women. Femara® is contraindicated in patients with known hypersensitivity to Femara® or any of its excipients.
Forward-looking Statement
The foregoing release contains forward-looking statements that can be identified by terminology such as "will file," "first," "only," "significant advantage," "helps," "benefit," or similar expressions, or by express or implied discussions regarding potential future sales 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 reach any particular sales levels. 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, industry, and general public pricing pressures; and other risks and factors referred to in the Company's current Form 20-F on file with the U.S. 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. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
