FDA OKs Evista for Breast Cancer Prevention in High-Risk Women

ROCKVILLE, Md., Sept. 17 -- The FDA has approved the osteoporosis drug raloxifene (Evista) for prevention of invasive breast cancer in high-risk or osteoporotic postmenopausal women.

That makes raloxifene, a selective estrogen receptor modulator, the second drug approved to reduce the risk of breast cancer. The other, tamoxifen, is in the same class.

Steven Galson, M.D., M.P.H., director of the FDA's Center for Drug Evaluation and Research, said the approval provided "an important option for women with heightened risk of breast cancer."

But, Dr. Galson cautioned, raloxifene can cause serious side effects and "the benefits and risks of taking [the drug] should be carefully evaluated for each individual woman."

Three clinical trials comparing raloxifene to placebo in 15,234 postmenopausal women found that raloxifene reduced the risk of invasive breast cancer by 44% to 71%.

In a fourth trial of 19,747 raloxifene was found to be as effective as tamoxifen for prevention of invasive breast cancer in high-risk women.

Results of that study, the STAR trial (Study of Tamoxifen and Raloxifene), made headlines when they were first reported at a National Surgical Adjuvant Breast and Bowel Project (NSABP) press conference.

The results were reported in greater detail when they were presented at the American Society of Clinical Oncology meeting in June 2006 and simultaneously published in the Journal of the American Medical Association. (See: ASCO: Evista or Tamoxifen? The Trade-Offs in Preventing Breast Cancer)

The STAR trial randomized women to daily treatment with 60 mg of raloxifene or 20 mg of tamoxifen, and the women were followed for almost four years.

In previous studies tamoxifen was shown to reduce breast cancer risk by 50%. In STAR "the ability of [Evista] to reduce breast cancer was equal to tamoxifen," said Victor Vogel, M.D., M.H.S., who was director of the STAR protocol.

But there were more cases of lobular carcinoma in situ or ductal carcinoma in situ among women taking raloxifene than among women randomized to tamoxifen.

At the ASCO meeting, the STAR trialists also revealed that women with intact uteri and women who were sexually active had more dose-limiting side effects with raloxifene than with tamoxifen.

A month later, the New England Journal of Medicine published results of the RUTH trial, a study of 10,000 postmenopausal women, that reported 44% reduction in the risk of breast cancer for raloxifene compared with placebo, but there was also a 49% increase in the relative risk of fatal stroke. (See: Evista Prevents Breast Cancer but Increases Risk of Fatal Strokes)

Noting that potential side effects of raloxifene include blood clots in the legs and lungs, and death due to stroke, the FDA said raloxifene should not be used in women with a history of blood clots in the legs, lungs, or eyes.

Other potential side effects include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating. Raloxifene should not be taken by premenopausal women and women who are or may become pregnant because it may cause harm to the unborn baby. In addition, raloxifene should not be taken with cholestyramine or estrogens.

Finally, the FDA said, patients should be reminded that raloxifene does not completely prevent breast cancer so a mammogram before initiating therapy and regularly thereafter are still recommended.