Novartis has submitted marketing applications in the United States, European Union and Switzerland for the use of Femara (letrozole) in the extended adjuvant treatment of early breast cancer in postmenopausal women who have completed standard adjuvant (post-surgery) tamoxifen therapy and remained disease-free.

These submissions mark the first time that data on a breast cancer therapy will be reviewed by health authorities for use of a medication following treatment with tamoxifen in the extended adjuvant setting.

The filings comprise results of the independent landmark MA-17 study, which was published expeditiously by the New England Journal of Medicine in the online edition in October 2003. Updated results from the trial will be presented during the "Best of Oncology" session on June 8.

The term extended adjuvant describes the period following standard adjuvant treatment with tamoxifen. During this stage, the ongoing risk of relapse remains significant for patients regardless of whether cancer cells were detected in the lymph nodes (called node positive) or not (node negative) at the time of diagnosis of early breast cancer. There is currently no clinically proven post-tamoxifen therapy available for the approximately one million women worldwide who take tamoxifen in any given year. Upon completion of tamoxifen therapy, these women are potential candidates for treatment with Femara.

"These filings represent a very important opportunity for Novartis Oncology to help fill a critical gap in breast cancer treatment," said Diane Young, MD, vice president, global head, Clinical Development, Novartis Oncology. "This is an important milestone in the clinical development program for Femara, and we look forward to the results of the BIG 1-98 early adjuvant study, which compares Femara and tamoxifen during the first five years of treatment after surgery. "

The filings were based on final data from an international, double-blind, randomized, multi-center study which included nearly 5,200 postmenopausal women with early breast cancer. The primary objective was to compare the disease-free survival of postmenopausal women taking Femara vs. placebo after approximately five years of post-surgery tamoxifen therapy. The interim published data showed, at a median interim follow-up of 28 months, that taking Femara after five years of adjuvant therapy with tamoxifen cut a woman's risk of recurrence nearly in half as compared with placebo (43 per cent reduced risk of recurrence; P=0.00008).

In addition, the estimated absolute improvement in disease free survival at four years was 6 per cent for patients taking Femara compared with placebo (93 per cent vs. 87 per cent). 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.

The interim data from MA-17 were so compelling that last fall an Independent Data Safety Monitoring Committee and the investigators unblinded the study so patients taking placebo could be offered the opportunity to switch to Femara. These patients had been on placebo for up to five years (median 24 months) when they were offered to switch to Femara. They continue to be followed under an amended protocol. MA-17 is being coordinated by the National Cancer Institute of Canada Clinical Trials Group and supported by Novartis.