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

June 6, 2006

ATLANTA ? Evista (raloxifene) may be a better choice than tamoxifen for preventing breast cancer in a high-risk post-menopausal woman if she has a uterus?and isn't sexually active.

ATLANTA, June 6 ? Evista (raloxifene) may be a better choice than tamoxifen for preventing breast cancer in a high risk post-menopausal woman if she has a uterus?and isn't sexually active.

Those are the kinds of trade offs facing physicians and women in light of the results from the STAR (Study of Tamoxifen and Raloxifene) trial, which were first reported at a press conference in April, but were dissected at the American Society of Clinical Oncology meeting here.

Two papers and an editorial on the STAR findings were also published online by the Journal of the American Medical Association.

Evista is less likely to cause uterine cancer so it may be a better choice for women with a uterus, but it is more likely to cause pain during intercourse and vaginal dryness, said Patricia Ganz, M.D., of the Jonsson Comprehensive Cancer Center at UCLA. Dr. Ganz was an author of the STAR quality-of-life analysis.

"I would advise that women should start on one drug and then re-assess in three months," said Dr. Ganz. "If the woman had a uterus, I would start her on [Evista], otherwise it would depend upon what is really important to a woman."

Women taking Evista were also more likely to report musculoskeletal symptoms (P=0.002) and weight gain (P

Harold J. Burstein, M.D., Ph.D. of the Dana-Farber Cancer Center in Boston said in an interview, "It may be that this drug [Evista] will turn out to be just not as effective against breast cancer as it first appears." Dr. Burstein was not involved in the trial but Dana-Farber was a participating center.

In any event, Dr. Wickerham said tamoxifen and Evista were equally effective in reducing invasive breast cancer in all subgroups "including women with a history of atypical hyperplasia or LCIS [lobular carcinoma in-situ]."

In terms of quality of life, the two drugs are also well-matched, said Dr. Ganz.

But unlike tamoxifen, which is known as "cancer drug," Evista is currently being prescribed by primary-care physicians to hundreds of thousands of women, Dr. Wickerham said, and that makes it uniquely appealing as a breast cancer primary prevention strategy.

Dr. Burstein agreed.

"Overall, tamoxifen is the most important drug in the history of oncology," he said. "It has saved more lives than any other drug." And when tamoxifen was compared to placebo for primary prevention of breast cancer, "it cut the risk in half in high risk women. But what that meant was that instead of these women having a 5% to 6% risk of breast cancer. They had a 2% to 3% risk?that's a 50% reduction but it doesn't look like much to a healthy women who is being asked to take a drug that causes hot flashes for five years."

Evista has the same benefit, Dr. Burstein said, but women are "already taking it to prevent osteoporosis. I'm not in advertising, but I can write the copy for this ad: on one side a woman says 'I'm at risk for osteoporosis.' On the other side, a woman says 'I'm at risk for breast cancer.' Into the picture comes the figure in the white coat who says: 'Here is one drug that will work for both of you.'"

Moreover cost may not be an issue, even though tamoxifen is available as a generic, while Evista is not. Dr. Wickerham declined to give a cost estimate, but Noah D. Kauff, M.D., of Memorial Sloan-Kettering Cancer Center in New York said he was told "that suggest Evista would cost a month versus a month for generic tamoxifen." Dr. Kauff offered that estimate during an ASCO press briefing where he was reporting data not related to the STAR findings.

Lilly, which markets Evista, has said it plans to seek FDA approval for labeling that indicates efficacy for breast cancer prevention, and Dr. Burstein predicted that Evista's role in prevention is likely to be significant.

Dr. Wickerham confirmed that an Evista-aromatase inhibitor trial is planned.

If Evista demonstrates non-inferiority for preventing invasive breast cancers in that trial, it may be come away a clear winner because Evista protects bones, while drugs like Arimidex (anastrozole) reduce bone mineral density.

Finally, in the JAMA editorial William J. Gradishar, M.D., and David Cella, Ph.D., of Northwestern University in Chicago wrote the "breast cancer chemoprevention sky now includes two shining STARs-tamoxifen and raloxifene. Although neither is a supernova, their benefits include prevention of breast cancer in postmenopausal women at increased risk and, in the case of raloxifene, reduction of fractures related to osteoporosis."

This study was supported by grants from the National Cancer Institute and by AstraZeneca and Eli Lilly.