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Letrozole Better Than Tamoxifen in Reducing Risk of Recurrence for Breast Cancer Survivors, IBSCG Study Published in New England Journal of Medicine Shows

BERNE, SWITZERLAND -- December 29, 2005 -- According to newly published data, postmenopausal women with hormone-sensitive early breast cancer receiving letrozole following surgery (adjuvant use) have a significantly greater chance of avoiding a recurrence than do women receiving tamoxifen. Letrozole is especially effective at preventing distant metastases. Women whose breast cancer returns or spreads to a distant site are known to be much more likely to die from their disease. These data, which appear in the December 29, 2005, issue of the New England Journal of Medicine, are the first published results of the landmark BIG 1-98 study.

In the study, women at higher risk for recurrence benefited most from letrozole. These patients included women whose disease had spread to the lymph nodes at initial diagnosis and those who had prior adjuvant chemotherapy.

"The publication of these findings in a journal as influential as the New England Journal of Medicine is likely to have a significant impact on the way postmenopausal women with hormone sensitive early breast cancer are treated after surgery," said Prof. Beat Thuerlimann, St. Gallen, Switzerland, BIG 1-98 Trial Study Chair. "We are especially encouraged by the substantial benefit seen in women at high risk for recurrence, which may ultimately lead to improved survival and outcomes in this group."

Compared with tamoxifen, letrozole significantly reduced the risk of:
ˇ breast cancer recurrence, the appearance of another breast tumor or other malignancy or death by 19% (P =.003)
ˇ distant metastases by 27% (P =.001)
ˇ recurrence in women with node-positive disease by 29% (P <.001)
ˇ recurrence in women who had prior chemotherapy by 30% (P =.01)

Methods and Additional Results

BIG 1-98 is a multinational phase 3 double-blind, randomized, multicenter trial being conducted in 27 countries. The study involves more than 8,000 postmenopausal women with early breast cancer who have hormone receptor-positive tumors. It is the only clinical trial designed to directly compare letrozole and tamoxifen as well as a sequencing of both agents during the first 5 years following breast cancer surgery.

A primary goal of the study is to determine if letrozole can reduce the risk of breast cancer recurrence compared with tamoxifen, as measured by disease-free survival (DFS). A DFS event was defined as a local, regional, or distant breast cancer relapse, occurrence of a second [non-breast] malignancy or death prior to cancer event. The newly published results document the effect on recurrence of initial treatment with tamoxifen versus initial
treatment with letrozole. Median follow-up was 26 months (half of the patients had been on study for 26 months or more), with more than 1,100 of those patients having completed 5 years of therapy. The results assessing the role of sequencing are expected in 2008.

Results further demonstrate that among the 4,003 patients in the letrozole group and 4,007 patients in the tamoxifen group:
ˇ 10.2% of the letrozole participants and 13.6% of the tamoxifen participants are projected to experience a breast cancer recurrence through 5 years
ˇ Overall survival favored letrozole, but the difference was not statistically significant
ˇ Letrozole led to a similar risk reduction in all participants with estrogen receptor positive status, regardless of progesterone receptor status

Additionally, letrozole and tamoxifen exhibited different safety profiles.

More common on tamoxifen were:
ˇ venous thrombosis and embolism (clots)
ˇ vaginal bleeding
ˇ endometrial abnormalities (changes in the lining of the womb)

More common on letrozole were:
ˇ bone fractures
ˇ joint pain

Invasive endometrial cancers were more frequent on tamoxifen (0.1% vs 0.3%, L vs T), while cardiac events (life-threatening or fatal) were more common on letrozole (0.8% vs 0.4%, L vs T), but both of these events were rare.

The study is being conducted under the umbrella of the Breast International Group (BIG), and is coordinated and managed by the International Breast Cancer Study Group (IBSCG). The IBSCG is an active member of the BIG organization. Novartis, the producer and distributor of letrozole (FemaraŽ) gave financial support.

About Early Breast Cancer

Early breast cancer (EBC) is defined as cancer that is localized to breast tissue and/or nearby lymph nodes. Worldwide, about 800,000 women are diagnosed with EBC each year. Primary therapy for EBC usually involves surgery to remove the tumor and surrounding tissue. Standard adjuvant therapy typically includes radiation and/or chemotherapy. If the tumor is hormone-receptor positive, women then receive endocrine treatment with 5 years of tamoxifen, which was for decades the standard of care for postmenopausal women until aromatase inhibitors such as letrozole offered further potential benefits.

About The International Breast Cancer Study Group

The International Breast Cancer Study Group (IBSCG) is a non-profit organization founded (as the "Ludwig Breast Cancer Study Group") in 1977. It is a cooperative group that has conducted numerous high quality and important clinical trials of adjuvant therapy for patients with operable breast cancer over 27 years. The IBCSG is headquartered in Berne as a foundation under Swiss law. With its network of investigators spanning five continents, the IBCSG has always been dedicated to innovative clinical research designed to improve the outcome of women with breast cancer.

About The Breast International Group

The BIG is an international non-profit organization established under Belgian law. As a communications network rather than a clinical research group in the traditional sense, BIG brings its members -- cooperative groups based in Europe, Australasia, Latin America and Canada that have affiliated centers around the world -- together in an organized way to collaborate in the design, conduct and interpretation of clinical trials in EBC.


SOURCE: The International Breast Cancer Study Group

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