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[Preciouslife1]

Femara First Aromatase Inhibitor to Indicate Survival Benefit Versus Tamoxifen When Taken for Five Years After Breast Cancer Surgery

Canada Newswire English - Dec. 11, 2008


- Femara* showed improved overall survival by 13% (P=0.08),
despite patients from the tamoxifen arm crossing over to Femara*therapy

- In a separate censored analysis excluding patients after they crossed over to Femara*, improved overall survival was 19%
- Long-term follow-up from major independent BIG 1-98 trial reinforces starting with Femara* as the optimal treatment strategy versus tamoxifen

http://www.therapeuticsdaily.com/news/article.cfm?contenttype=sentryarticle&contentvalue=1872529&channelID=28
DORVAL, QC, Dec. 11 /CNW Telbec/ - New long-term data from a major international breast cancer study demonstrates that treatment with Femara* (letrozole) may provide an important survival benefit compared to treatment with tamoxifen in early-stage breast cancer.

The findings from the Breast International Group (BIG) 1-98 trial, presented today at the 31st Annual San Antonio Breast Cancer Symposium (SABCS), suggests that Femara*, when taken as a monotherapy for five years following surgery has the potential to increase the overall survival rate by 13% (P=0.08) compared to tamoxifen only, in postmenopausal woman with hormone receptor-positive (HR+) early-stage breast cancer(1). The results make Femara* the first aromatase inhibitor to suggest a survival benefit versus tamoxifen in the monotherapy setting immediately following surgery.

"These data reinforces the use of Femara* in adjuvant treatment of early breast cancer in post-menopausal women.
No other aromatase inhibitor in the upfront adjuvant setting has suggested this level of improvement in overall survival versus five years of tamoxifen," says Dr. Kathleen Pritchard, Senior Scientist, clinical epidemiology - cancer program, Sunnybrook Research Institute (SRI), in Toronto, Ontario.

The results are from a protocol-defined Intent-to-Treat (ITT) analysis (median follow-up of 76 months) of the Femara* and tamoxifen monotherapy arms in the BIG 1-98 study. While not statistically significant, the suggested survival benefit from the ITT analysis is important considering that approximately 25% of patients in the tamoxifen arm selectively crossed over to Femara* therapy. This cross-over took place after the tamoxifen arm was unblinded in 2005 and showed superiority of Femara* monotherapy over tamoxifen monotherapy in improving disease-free survival and reducing the risk of recurrence.

When correcting for this cross-over in the tamoxifen arm, a 19% reduction in risk of death (HR=0.81, 95% CI: 0.69-0.94) was observed in favour of Femara*.

Spanning the years from 1998 to 2008, BIG 1-98 is the only clinical trial designed to explore both a head-to-head comparison of an aromatase inhibitor with tamoxifen during the first five years following breast cancer surgery and the sequencing of both agents to determine the most effective approach to minimizing the risk of disease recurrence.

BIG 1-98 Sequential treatment analysis (STA)

The BIG 1-98 study also included two early sequential treatment strategies: Femara* before or after tamoxifen after surgery. An analysis of outcomes among women in the monotherapy arms compared to those in the sequential arms (from randomization) revealed that sequencing hormone therapy following surgery is not superior to five years of Femara* alone and supports the benefit of starting Femara* adjuvant treatment for five years after surgery versus tamoxifen in patients at higher risk of relapse.

The five-year disease-free survival rates for the three groups of patients in the STA were 87.9% for those patients receiving Femara* only, 86.2% for those patients receiving two years of tamoxifen followed by three years of Femara* and 87.6% for those patients receiving two years of Femara* followed by three years of tamoxifen.

Additional BIG 1-98 data

Beyond the increase in overall survival of 13% (P=0.08, HR=0.87, 95% CI: 0.75-1.02) for Femara* patients seen in the ITT analysis, Femara* demonstrated significant long-term benefit in reducing the risk of disease free survival events by 12% (P=0.03, HR=0.88, 95% CI: 0.78-0.99) and reducing the risk of distant metastases by 15% (P=0.05, HR=0.85, 95% CI: 0.72-1.00) compared with tamoxifen.

About the BIG 1-98 study

This Phase III, randomized, double-blind, controlled clinical trial enrolled postmenopausal women with early breast cancer, in 27 countries(1).

Patients were randomly assigned one of four treatment regimens: (1) five years of tamoxifen only; (2) five years of Femara* only; (3) two years of tamoxifen followed by three years of Femara*; (4) two years of Femara* followed by three years of tamoxifen. In 1998 the first cohort began enrolling patients to receive either Femara* or tamoxifen alone. In 1999, the second cohort (solely contributing to the Sequential Treatment Analysis) began enrolling patients to receive Femara* or tamoxifen alone, tamoxifen followed by Femara* or Femara* followed by tamoxifen (n=6,182 patients). Combined, the monotherapy arms of the trial included 4,922 patients who were randomly assigned either Femara* or tamoxifen treatment(1). The Primary Core Analysis, reported in 2005, included all 8,010 patients enrolled in the trial.

The primary endpoint of the study was disease-free survival (DFS), defined as the time from randomization to the first of one of the following events: recurrence at local, regional, or distant sites; a new invasive cancer in the contralateral breast; any second, non-breast cancer; or death without a prior cancer event, which is similar but not identical to the endpoint definitions used in other AI adjuvant trials. Other endpoints included time to breast cancer recurrence (including invasive contralateral breast cancer, ignoring second (non breast) malignancies, and censoring deaths prior to cancer event), time to distant breast cancer recurrence (time to breast cancer recurrence but ignoring local, regional and contralateral breast events), and overall survival.

With the long-term follow-up in the analysis conducted more than 10 years after the start of the study, adverse events for Femara* and tamoxifen were found to be consistent with the known safety profiles of both drugs. Patients will be monitored for the rest of their lives to track disease status, safety and overall survival(2).

About Femara* (letrozole)

Femara* belongs to a class of medications called aromatase inhibitors. In postmenopausal women, the body produces estrogen exclusively by transforming androgen into estrogen through the action of an enzyme called aromatase. Aromatase inhibitors, including Femara*, work by binding to the aromatase enzyme to block the production of estrogren, thereby reducing the growth of the tumor.

In 2006 the Therapeutic Products Directorate of Health Canada (TPD) granted a Notice of Compliance with Conditions (NOC/c) for Femara* for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. The conditional approval was based on earlier results of the BIG 1-98 study. Femara* is also approved in Canada for use in the extended adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women who have received approximately five years of prior standard adjuvant tamoxifen therapy; the first-line therapy in postmenopausal women with advanced breast cancer; and 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.

Femara* is currently available in more than 100 countries worldwide.
For current Canadian prescribing information including safety information, please visit www.novartis.ca.


About Novartis Canada

Novartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2007, the Company invested over $86 million in research and development. Novartis Pharmaceuticals Canada Inc. employs approximately 800 people in Canada and its headquarters are located in Dorval, Quebec. It was named one of the "50 Best Employers in Canada" in 2008. For further information, please consult www.novartis.ca.