Letrozole provides a better disease free survival than tamoxifen,results show
Jan 27, 2005, 16:45, Reviewed by: Dr.
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By Akanksha,Pharmacology Correspondent,
First results of major study show that Femara�(letrozole) provides a disease free survival advantage vs. tamoxifen in adjuvant treatment of early breast cancer.
The Breast International Group (BIG) 1-98 trial did a head-to-head comparison of letrozole with tamoxifen in more than 8 000 women treated at a median follow-up of only 26 months.
The study showed that adjuvant use of letrozole in postmenopausal women with hormone receptor-positive early breast cancer was associated with a significant 19% reduction in risk of relapse (p=0.003); especially reducing the risk that the cancer would spread to other parts of the body (distant metastases) by 27%, compared with the reductions offered by tamoxifen (p=0.006) according to an international study presented today by the International Breast Cancer Study Group.
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 tumor, or death from any cause.
"The biggest fear of women who have battled breast cancer is that their breast cancer might return," said PD Dr. Beat Th�rlimann, MD, Scientific Secretary General, Therapy of Early Breast Cancer Senology Center of Eastern Switzerland, Kantonsspital St.Gallen. "Convincing results from this very large study show that letrozole helps more women remain cancer free when compared to tamoxifen."
For the study,postmenopausal women with early breast cancer in 27 countries enrolled in the phase III, randomized, double-blind, controlled clinical trial, supported by Novartis.
There was a statistically significant reduction of 17% 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% reduction in risk of death in favor of letrozole 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 for the use of letrozole in the extended adjuvant setting. Letrozole is the only aromatase inhibitor shown to be effective in both the adjuvant and extended adjuvant settings. The term extended adjuvant describes the period following standard adjuvant treatment with tamoxifen. Letrozole is approved for extended adjuvant treatment of early breast cancer in 20 countries worldwide.
"This is exciting news for breast cancer patients and Novartis. Letrozole 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 letrozole 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.
In this trial, patients treated with letrozole had significant reductions 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 letrozole. As expected with estrogen deprivation therapy, the number of women reporting new bone fractures to date was 5.8% on letrozole and 4.1% on tamoxifen. Grade 3-5 thromboembolic events were more common in tamoxifen treated patients. In patients whose breast cancer did not recur, more deaths due to stroke were reported in letrozole treated patients than tamoxifen treated patients (7 vs. 1) as well as cardiac causes (26 vs. 13). These events combined with all deaths from causes other than recurrence of breast cancer were not statistically significant. The median age of women who died without experiencing a previous cancer event was 70 compared with a median age of 61 of all women in the study. Further 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 considered. Overall, more patients in the study died on tamoxifen than letrozole.
BIG 1-98 is the only clinical trial designed to incorporate both a head-to-head comparison of letrozole 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, letrozole for five years, tamoxifen for two years followed by letrozole for three years, and letrozole 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.
Letrozole is a leading once-a-day oral aromatase inhibitor that is indicated for first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer and for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy, and as neo-adjuvant (pre-operative) therapy.
Letrozole is approved for extended adjuvant treatment of early breast cancer in postmenopausal women who have completed adjuvant tamoxifen therapy in 20 countries worldwide. Letrozole is currently available in more than 80 countries worldwide. Not all indications are available in every country.
The most common adverse events experienced with Letrozole 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, arthritis/arthralgia, and weight increase.
Letrozole is contraindicated in women who are pregnant or breast-feeding as well as in premenopausal women. It is also contraindicated in patients with known hypersensitivity to letrozole or any of its excipients.
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Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2004, the Group's businesses achieved sales of USD 28.2 billion and a net income of USD 5.8 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 81 400 people and operate in over 140 countries around the world. For further information please consult the company web site.
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