Femara

Femara (chemical name: letrozole) has been used for many years as an adjuvant treatment (given after the main treatment) for post-menopausal women with advanced disease that is hormone-receptor-positive. In October 2004, the U.S. Food and Drug Administration (FDA) approved Femara for extended adjuvant use in women with early-stage, hormone-receptor-positive breast cancer after 5 years of tamoxifen. "Extended adjuvant use" means that it is approved for longer than 5 years, which is the standard length of time to take hormonal therapy. The approval for extended use was based on an international study of more than 5,000 post-menopausal women.

The MA–17 study included 1,404 women in Canada, 3,607 in the United States, and 176 in Europe. All were post-menopausal, had taken tamoxifen for between 4.5 and 6 years after diagnosis and treatment of their original cancer, and had been off tamoxifen for less than 3 months when the study began. The women were divided into two groups:

• One group took Femara for another 5 years.
• One group took a dummy pill, or placebo, for 5 years.

The women were seen by their doctors every 6 months in the first year, and once a year after that. Side effects and physical findings were noted at each visit.

The researchers found that, compared to women taking Femara, nearly twice as many women taking the placebo had the cancer come back. Overall, Femara reduced the risk of recurrence by 43%. After an average of 4 years, 13% of the women taking the placebo, but only 7% of those taking Femara, had the cancer come back. Women taking Femara had fewer recurrences in the breast where the cancer had occurred, in the opposite breast, and in internal organs.

In late August 2003, researchers stopped the study earlier than they had originally planned. The results of taking Femara were so beneficial that the researchers wanted all the women in the study to have the opportunity to take the medication instead of the dummy pill.

After an analysis of information from about 1,500 of the MA-17 trial participants who decided to switch to Femara from the placebo after the study was stopped, the researchers announced in 2008 that taking Femara after taking tamoxifen for 5 years reduced the risk of recurrence, even in women who started Femara up to 7 years after finishing tamoxifen. Women who took Femara for 5 years after having taken tamoxifen for 5 years reduced their risk of the breast cancer coming back by 63%. Three years after the research ended, about 5% of the women who took only tamoxifen had the cancer come back, while only 2% of the women who took tamoxifen then Femara did.

Another, more recent study of 8,000 post-menopausal women has looked at the use of Femara in women with early-stage breast cancer. The BIG (Breast International Group) 1-98 study began in 2000 and will continue until 2008. This large trial is comparing Femara to tamoxifen. Researchers are looking at the safety of the two drugs and their ability to reduce the risk of breast cancer coming back. They are also looking at how long the women taking each medicine live, and how long they live without the cancer coming back.

The women in the study are divided into 4 groups, depending on what medicine they took after surgery and for how long:

• Some are taking tamoxifen for 5 years.
• Some are taking Femara for 5 years.
• Some are taking tamoxifen for 2 years and then switching to Femara for 3 years.
• Some are taking Femara for 2 years and then switching to tamoxifen for 3 years.

After 2 years of follow-up, compared to the women who took tamoxifen, the women who took Femara had a significantly lower risk of recurrence and increased length of life without the cancer coming back. Women who took Femara had an increased risk of bone breaks, but a lower risk of blood clots. The results of the "switching" part of this study (from tamoxifen to Femara and from Femara to tamoxifen) are expected to be released in 2008.

In December 2005, an update to the 1-98 trial was reported in the New England Journal of Medicine. Femara was shown to have many benefits over tamoxifen.

• Femara was found to reduce the risk of cancer coming back by 21% more than tamoxifen.
• It also was proven to reduce the risk of the cancer spreading throughout the body (metastases) by 27% more than tamoxifen.
• Women who had received chemotherapy and those who had more aggressive breast cancers (lymph-node involvement)—received the most benefit from using Femara.

As a result of this evidence for Femara's benefits, the FDA approved Femara for use after surgery in post-menopausal women with hormone-receptor-positive breast cancer.