FDA Advisers Recommend Raloxifene (Evista) for Prevention of Breast Cancer

ROCKVILLE, Md., July 25 -- An FDA advisory panel has recommended that the agency approve raloxifene (Evista) for prevention of breast cancer in high-risk postmenopausal women.

For that indication, the panel voted 10 to 4. By a closer vote -- 8 to 6 -- the panel said raloxifene's label should be amended to allow its use for prevention of breast cancer in women with osteoporosis.

Raloxifene, a selective estrogen receptor modulator (SERM), was approved in 1997 for treatment and preventions of osteoporosis.

The FDA is expected to act by the end of September. Although the agency is not required to follow the advice of its advisory panels, it generally does.

David Harrington, Ph.D., of the Dana-Farber Cancer Institute in Boston, noted that tamoxifen, although effective, is also difficult to tolerate. Raloxifene, by comparison, is well tolerated by most women and approval of the drug would offer women another option.

A trial of 19,747 women was reported in April 2006 showing that raloxifene was as effective as tamoxifen for preventing 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.

(ASCO: Evista or Tamoxifen? The Trade-Offs in Preventing Breast Cancer)

The STAR trial randomized women to daily treatment with 60 mg of Evista 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 Evista than among women randomized to tamoxifen.

The START researchers have consistently downplayed this, saying this difference (81 cases in the Evista arm versus 57 cases among women taking tamoxifen) were not "really cancer., not really life-threatening disease," said Leslie Ford, M.D., associate director for clinical research at the National Cancer Institute's Division of Cancer Prevention.

Still, Len Lichtenfeld, M.D., deputy chief medical officer for the American Cancer Society, said that lobular carcinoma in situ and ductal carcinoma in situ are not insignificant events for women who are diagnosed with these conditions, which are often termed "pre-cancers". He noted that both "increase the risk of invasive cancer and both conditions are treated." (Evista Prevents Invasive Breast Cancer in High Risk Post-Menopausal Women)

In June, 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. (Evista Prevents Breast Cancer but Increases Risk of Fatal Strokes)

Some panelists voiced concern about safety issues raised in those trials, which prompted the panel to recommend that the FDA establish limits for how long women should take raloxifene. They also said the FDA should require post-marketing studies to track safety.

One advocacy group, Breast Cancer Action, which is based in San Francisco, said the benefits of the drug don't outweigh the risks for most women.

In a statement, Barbara Brenner, executive director of Breast Cancer Action, said the "relatively few number of women who may avoid breast cancer by taking raloxifene is far outweighed by the risk of blood clots and strokes from the drug that thousands of other women will experience."