Femara Approved as Adjuvant Rx for Early Breast Cancer

ROCKVILLE, Maryland-Femara (letrozole, Novartis) has received FDA approval for use in treating early breast cancer in postmenopausal women following surgery. The agency based its approval on findings from the BIG I-98 study, the only trial designed to compare the safety and efficacy of Femara vs tamoxifen when used as adjuvant therapy in postmenopausal women with hormone-receptor-positive early disease.

Results from the randomized multinational trial showed that Femara reduced the risk of breast cancer recurrence by an additional 21%, compared with the reduction seen with tamoxifen (P = .002). The Femara patients also had a 27% reduction in the risk of distant metastases (P = .0012). Other key findings showed that Femara reduced the risk of disease recurrence by 29% in women whose breast cancer had spread to the lymph nodes at diagnosis, and by 30% in women who had undergone chemotherapy. In these two high-risk groups, the risk of distant metastases fell by 33% and 31%, respectively.

"One of the greatest fears confronted by women who have been treated for early breast cancer is that their cancer will come back," said Matthew Ellis, MD, PhD, director, Breast Cancer Program, and associate professor, Medical Oncology Division, Washington University, St. Louis. "With Femara, we now have an option that can help address that fear early on, even in the patients who we know face the greatest risk of recurrence. Femara has proven to be a very important option in the treatment paradigm for postmenopausal women with hormone-sensitive early breast cancer."

Femara is a once-a-day oral aromatase inhibitor. FDA initially granted the drug marketing approval in July 1997 for the treatment of advanced breast cancer in postmenopausal women. It is now approved for that use in more than 90 nations, according to Novartis.

The BIG I-98 trial was a 5-year phase III, double-blind study conducted in 27 countries, in which researchers randomized 4,003 early-stage breast cancer patients to Femara and 4,007 to tamoxifen. At a median follow-up of 25.8 months, 351 recurrences had occurred in the Femara group and 428 in the tamoxifen arm, a significant difference that yielded 5-year, disease-free survival estimates of 84.0 months and 81.4 months, respectively, for the two treatment groups.

"Femara has consistently demonstrated superiority against tamoxifen as first-line therapy in women with locally advanced or metastatic breast disease, as well as in the adjuvant setting," said Diane Young, MD, vice president and global head of clinical development at Novartis Oncology. "In addition, Femara provides a notable benefit to patients who are at especially high risk of having their breast cancer return."

Adverse events reported in the adjuvant setting generally proved mild to moderate in both Femara- and tamoxifen-treated patients. They included hot flashes (33.7% vs 38%, respectively), joint pain (21.2% vs 13.5%), night sweats (14.1% vs 13.5%), and weight gain (10.7% vs 12.9%). Thromboembolisms, endometrial cancer, and vaginal bleeding occurred more often in the tamoxifen group. The Femara arm experienced a higher incidence of skeletal problems, cardiac events, and hypercholesterolemia.

Results from the BIG I-98 trial appeared in the December 29, 2005, issue of the New England Journal of Medicine (353:2747-2757, 2005), the day after FDA announced it had approved the new indication for Femara.