New Long-term Data Published in Journal of Clinical Oncology Support That Femara Is More Effective Than Tamoxifen
• BIG 1-98 four-year results show Femara further reduced risk of early breast cancer returning compared with tamoxifen
• Femara significantly reduced risk of cancer spreading to other parts of the body
EAST HANOVER, NJ, Feb. 20, 2007 – Long-term follow-up data from the independent Breast International Group (BIG) 1-98 trial support earlier findings that Femara (letrozole tablets) is more effective than tamoxifen as initial post-surgery therapy for early breast cancer. The updated study results were published in the February 10 issue of the Journal of Clinical Oncology (SEE ATTATCHMENT).
At a median follow-up of more than four years (51 months), Femara reduced the risk of breast cancer recurrence by an additional 18% as well as the risk of distant metastases (the breast cancer spreading to other parts of the body) by an additional 19% versus tamoxifen in postmenopausal women with hormone-sensitive early breast cancer. The data on distant metastases is particularly important because cancer that spreads to other parts of the body increases the likelihood that a woman will die from the disease.
This new analysis included nearly 5,000 women assigned to receive five years of Femara or tamoxifen. More than 1,200 women completed five years of treatment. The primary core analysis conducted at a median follow-up of 26 months also included women assigned to receive Femara or tamoxifen for two years followed by three years of the other agent.
“The four-year data in this population is consistent with our initial findings that letrozole may help protect women from breast cancer recurrence and distant spread better than tamoxifen,” said Alan Coates, M.D., clinical professor, School of Public Health, University of Sydney, Australia, who authored the study. “The publication of this longer-term analysis from BIG 1-98 will help physicians more clearly evaluate the contribution of letrozole in managing breast cancer.”
The current analysis strengthens the evidence of the broad range of patients who may benefit from Femara. Femara significantly improved disease-free survival (a measure of disease recurrence) in the overall study population. In women with node positive disease, Femara significantly reduced the risk of recurrence by a further 23% versus tamoxifen. In women who received chemotherapy, the reduction was a further 26%. These two groups of women are more likely to have their breast cancer return. Women with node negative disease and those who did not receive chemotherapy were also evaluated.
An improvement in disease-free survival in node negative patients also emerged with longer follow-up. In the current analysis, Femara reduced the risk of breast cancer coming back in this group of women by 12% versus 4% observed at the primary core analysis, though this did not achieve statistical significance. Women with node negative disease tend to experience recurrence later than women with node positive disease.
The overall safety profile was consistent with the primary core analysis. Extensive and rigorous collection of safety data in this patient population over four years showed that adverse events for both Femara and tamoxifen were similar to previously reported results from this trial.
“As data from BIG 1-98 mature, they consistently provide physicians with evidence of the compelling benefits of Femara as adjuvant therapy over tamoxifen, particularly the significant reductions in distant disease spread,” said Diane Young, M.D., vice president, head, Global Medical Affairs, Novartis Oncology. “These data may help guide physicians’ treatment decisions when choosing between aromatase inhibitors.”
Femara is the only medicine in its class indicated for women with hormone-dependent breast cancer taken as either initial treatment immediately after surgery (adjuvant setting) or after they have completed five years of tamoxifen therapy (extended adjuvant setting).
About BIG 1-98
BIG 1-98 is the only clinical trial that incorporates both a head-to-head comparison and a sequencing of Femara and tamoxifen as adjuvant treatment for postmenopausal women with hormone receptor-positive breast cancer. The results of the primary core analysis of the head-to-head comparison based on a median follow-up of 26 months were published in the December 29, 2005 issue of the New England Journal of Medicine. The BIG 1-98 trial was conducted by the International Breast Cancer Study Group (IBCSG) with many independent centers and was supported by Novartis.
Femara is a once-daily oral prescription medication approved for the adjuvant (following surgery) treatment of postmenopausal women with hormone receptor-positive early breast cancer. The benefits of Femara in clinical trials are based on 24 months of treatment. Further follow-up will be needed to determine long-term results, including safety and efficacy.
Femara is also approved for the extended adjuvant treatment of early stage breast cancer in postmenopausal women who are within three months of completion of five years of adjuvant tamoxifen therapy. The benefits of Femara in the extended adjuvant setting are based on 24 months of treatment. Further follow-up will be needed to determine long-term results, including side effects.
Femara is also approved for the 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.
Important safety information
Patients must be postmenopausal to take Femara. Patients should talk to their doctor if they are allergic to Femara or any of its ingredients. Patients should not take Femara if they are pregnant as it may cause fetal harm. Some women reported fatigue and dizziness with Femara. Until patients know if Femara affects them, they should use caution before driving or operating machinery. Some patients taking Femara had an increase in cholesterol. Additional follow-up is needed to determine the risk of bone fracture associated with long-term use of Femara.
In the adjuvant setting, commonly reported side effects are generally mild to moderate. Side effects that are comparable between Femara and tamoxifen include night sweats, weight gain, nausea, and tiredness. Side effects seen more often with tamoxifen vs. Femara were hot flashes and vaginal bleeding. Joint pain was experienced more often with Femara vs. tamoxifen. The incidence of stroke was 1.1% for women on Femara and 1.0% for women on tamoxifen, and the incidence of other cardiovascular events was 6.6% for Femara vs. 6.2% for tamoxifen. The percentage of women on Femara reporting bone fracture was 5.6% vs. 4% for women on tamoxifen. The percentage of women reporting osteoporosis was 2% for Femara vs. 1.1% for tamoxifen.
In the extended adjuvant setting, commonly reported side effects are generally mild to moderate. Those seen more often with Femara vs. placebo were hot flashes (50% vs. 43%), joint pain (22% vs. 18%) and muscle pain (7% vs. 5%). Other side effects, which were comparable to placebo, include fatigue (34% vs. 32%), swelling due to fluid retention (18% vs. 16%), headache (20% vs. 20%), increase in sweating (24% vs. 22%) and increase in cholesterol (16% vs. 16%). The percentage of patients on Femara vs. placebo reporting a fracture was 5.9% vs. 5.5%. The percentage of patients reporting osteoporosis was 6.9% vs. 5.5%. Bisphosphonates, drugs to increase bone strength, were given to 21.1% of Femara patients and 18.7% of placebo patients.
In the metastatic setting, commonly reported side effects are generally mild to moderate and may include bone pain, hot flashes, back pain, nausea, joint pain, shortness of breath, fatigue, coughing, constipation, limb pain, chest pain, and headache.
The foregoing release contains forward-looking statements that can be identified by terminology such as “likelihood,” “may,” “will,” “more likely,” or similar expressions, or by express or implied discussions regarding 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 reach any particular sales levels. Neither can there be any guarantee regarding the long-term impact of a patient’s use of Femara. In particular, management's expectations regarding Femara could be affected by, among other things, unexpected clinical trial results, including additional analysis of existing clinical data, or new clinical data; unexpected regulatory actions or delays or government regulation generally; competition in general; increased government, industry, and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; 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.
For more information
Additional information regarding Femara or Novartis Oncology can be found on the websites www.femara.com or www.novartisoncology.com.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS), a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group’s businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 101,000 associates and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.
Dana Kahn Cooper
Posted: February 2007