July 12, 2006 -- Hopes that the osteoporosis drug Evista would offer women a clearly safer alternative to tamoxifen for breast cancer prevention have been dashed by findings from a long-awaited study, researchers say.
The postmenopausal women in the trial all had risk factors for coronary heart disease and were considered at risk for heart attack and stroke.
Women who took Evista did develop significantly fewer breast cancers than women randomly assigned to take a placebo (medicine-free treatment) in the approximately five-year study. But they also had significantly more fatal strokes and potentially dangerous blood clots.
The study appears in tomorrow's issue of the New England Journal of Medicine. It was funded, in part, by Evista manufacturer Eli Lilly. Eli Lilly is a WebMD sponsor.
"This study highlights the fact that we cannot look at one condition or one outcome when we consider a drug for prevention," says Lori Mosca, MD, PhD, researcher on the "Raloxifene Use for the Heart" (RUTH) study.
Mosca tells WebMD that she considers the findings "somewhat disappointing."
"This trial was pretty much a wash in terms of benefits vs. risks in this population [at high risk for cardiovascular events]," she says. "The bar has to be higher for drugs used for prevention of diseases than for drugs used to treat them. I think there needs to be a clear indication of benefit."
No Heart Benefits
As the name suggests, the original goal of the RUTH trial was to determine if Evista could help prevent heart attacks and strokes in women at high risk for heart disease.
Evista is in a class of drugs known as selective estrogen receptor modulators (SERMs). Tamoxifen, which is also a SERM, is approved for breast cancer prevention in high-risk women and for the treatment of breast cancer.
A total of 10,101 postmenopausal women with multiple risk factors for heart disease participated in the RUTH trial; roughly half took Evista every day for an average of five years and the other half unknowingly took an identical-looking placebo.
The number of cardiac events experienced by the two groups was similar. But significantly fewer breast cancers were diagnosed in the Evista users than in those on placebo (40 vs. 70).
Deaths from any cause were also similar in both groups, and the two groups had roughly the same number of strokes. But Evista users had significantly more fatal strokes (59 vs. 39) and potentially dangerous blood clots (103 vs. 71 events) than women taking placebo.
Mosca points out that women taking the SERM also had a higher incidence of several nonlife- threatening, but troubling, side effects, including hot flashes and leg cramps.
The RUTH trial results may serve to dampen the optimism that surrounded Evista following the release of another study three months ago.
The Study of Tamoxifen and Raloxifene (STAR) trial -- one of the largest breast cancer prevention trials ever conducted -- found Evista to be as effective as tamoxifen for preventing breast cancers.
And unlike tamoxifen, Evista did not increase the risk of developing uterine cancers. There was also some suggestion that Evista was safer in terms of blood clot and cataract risk. The two treatment groups had roughly the same incidence of strokes, heart attacks, and bone fractures.
At the time, STAR researcher D. Lawrence Wickerham, MD, called Evista the clear "winner" of the head-to-head comparison trial.
But women's health researcher Marcia Stefanick, PhD, of Stanford University, says the STAR trial had no clear winner.
"I think that at best the findings represented a draw," she says. "The hope was that raloxifene would offer the benefits of tamoxifen without the risks, but that isn't what happened."
In an editorial examining the RUTH findings, Stefanick writes that identifying who should and should not take tamoxifen or Evista for breast cancer prevention remains problematic.
"For now, there is no magic bullet that can reduce the risks of major health problems related to estrogens and aging without introducing other potentially serious health concerns," she wrote.
She tells WebMD that drug makers are continuing the search for a better SERM for breast cancer prevention.
"If raloxifene is better [than tamoxifen], I believe it is just a little bit better," she says. "And you have to remember that far more women die from stroke than from breast cancer. More women die from heart disease than all cancers put together."