Earlier this month, women at risk of developing breast cancer received a limited reason for hope: A drug called tamoxifen was found effective at preventing breast cancer, but it is associated with increased rates of uterine cancer.
Now comes a potentially bigger breakthrough. As-yet-unreleased results of clinical trials of a drug called Evista indicate that it, too, is effective at preventing breast cancer-without any increase in the risk of uterine cancer.
Trials of Evista as a cancer combatant go back only two years-too short a time to elicit anything more than very cautious optimism from scientists, and skepticism from some health officials. "Two years is nothing," says Cynthia A. Pearson, executive director of the National Women's Health Network, a consumer group. What is known about the drug "can change in five years or 10 years."
Designer Drugs
Yet whether or not tamoxifen and Evista become widely used breast-cancer weapons, their performance in clinical trials is prompting some researchers to envision a turning point in the battle against several cancers. In the minds of some top researchers, prevention with pharmaceuticals, as opposed to conventional treatment after diagnosis, is becoming a real possibility.
"We're entering a new period in which we may have the ability to consider and test drugs to lower the incidence of cancers the way we lower cholesterol," says Richard D. Klausner, director of the National Cancer Institute. Calling Evista and other such drugs "the beginning of the era of designer hormones," he adds, "we need to enter into this new era very cautiously."
Caution is difficult because the stakes are so high. This year, breast cancer alone will strike an estimated 178,000 women in the U.S. and kill 43,500 --some of them genetically predisposed to the cancer. Millions of others live in fear of it, so that even the most guarded talk of a prevention pill is bound to raise hopes-and not only among potential sufferers.
Market Impact
Although the maker of Evista, Eli Lilly & Co., has tried to keep its clinical-trial results under wraps, The Wall Street Journal and at least one securities analyst have obtained some of the data. On Friday, after Morgan Stanley analyst Paul Brooke wrote about some of the highly promising Evista results, investors immediately drove shares of Lilly up $5.125, to close at $68.375 in composite trading on the New York Stock Exchange.
Many researchers share that excitement. After all, the news about raloxifene, the generic name for Evista, is coming only days after tamoxifen was declared the first drug in history to be able to prevent new breast cancers, at least over a four-year period.
"I'm excited about" raloxifene, says Funmi Olopade, oncologist and director of the cancer-risk clinic at the University of Chicago Medical Center. "My take on raloxifene is that it may be an improvement over tamoxifen. This means there are going to be more options for women."
Both Evista and tamoxifen belong to a class of drugs known as selective estrogen receptor modulators, or SERMs. These drugs, sometimes called designer estrogens, have been developed to replace traditional estrogen therapy. That therapy strengthens bones, improves cardiac health and is believed to provide some protection against Alzheimer's disease. But in older women, it also is associated with an increase in the incidence of uterine cancer and possibly of breast cancer. Even so, the leading estrogen-replacement therapy for older women, American Home Products Co.'s Premarin, is a $1 billion-a-year drug.
Only the Good Stuff
The SERM drugs are meant to achieve the positive effects and avoid the dangerous ones. Among the companies with such drugs in their pipelines are Glaxo Wellcome PLC, Pfizer Inc., SmithKline Beecham PLC and Zeneca Group PLC, which sells tamoxifen under the brand name Nolvadex.
In Indianapolis, Lilly officials decline to talk about Evista as a breast-cancer combatant. They can't. Because Evista is approved currently as a drug only for osteoporosis, Lilly isn't allowed to say anything publicly suggesting that Evista reduces breast-cancer risk. The company and its sales representatives are allowed to say only that Evista doesn't increase breast cancer, and that it increases bone density and thus helps prevent osteoporosis in older women.
But certainly, Lilly officials would love to see Evista become the Prozac of the breast-cancer battle. Early next century, the patent on Lilly's leading product, the antidepressant Prozac, will expire, and Lilly needs something to replace it. It has a good start with Zyprexa, which in just 18 months on the market has become the No. 1 schizophrenia treatment, with estimated sales this year of more than $1 billion.
But Prozac will rack up sales this year of an estimated $2.8 billion, and Lilly will probably need more than one drug to replace it.
As an osteoporosis preventive, Evista had estimated sales of $30 million in its first full quarter on the U.S. market, ended March 31. But its most promising use has been quietly under study at University of California at San Francisco, Northwestern Memorial Hospital in Chicago and Memorial Sloan-Kettering Cancer Center in New York, among other locations.
The Evista trials pose the same question as the tamoxifen trials: Can this drug prevent breast cancer?
Big Groups
The trials of tamoxifen, a failed contraceptive that had proven effective at treating breast cancer, lasted four years. These trials showed that in healthy women at high risk of breast cancer, tamoxifen lowered the incidence of the disease by 45%, compared with women who had taken a placebo. The tamoxifen trials involved a large number of women, 13,338, and the Evista trials even more, about 19,000.
The Evista trials don't provide a solid comparison. The Evista work has been conducted on a general population of women who have gone through menopause and who don't necessarily have a higher cancer risk. And the Evista trials, which are continuing, have been going on for about half as long.
But the results so far could hardly be more promising. In one trial, UCSF physician Steven R. Cummings recorded a "relative risk" of breast cancer of 0.26 in women who took Evista compared with a control group. That means a reduction in the incidence of new breast cancers of about 74% in the women who took Evista over an average of two years and five months.
During the study, twice as many women were given Evista as those in a control group, who received only a placebo. Yet only 11 of the women on Evista, or 0.21%, had new breast cancers confirmed during the study. Meanwhile, 21 of the women assigned to placebo, or 0.82%, got new breast cancers. Dr. Cummings declined to discuss the results.
In the tamoxifen trials, users developed uterine cancer at more than twice the rate of placebo takers. In the Evista trials, users had a lower rate of uterine cancer than those who took placebos.
A head-to-head comparison of Evista and tamoxifen is expected to begin in the fall, under the direction of the National Cancer Institute. But already, the evidence that drugs can be designed to protect organs from cancer-inducing hormones is exciting some usually reserved scientists.
"The tamoxifen and Evista studies represent one of the biggest breakthroughs in cancer research in history," says Larry Norton, director of the breast center and head of medical oncology at Memorial Sloan-Kettering.
Next: Prostate Cancer
"If we can convert the breast into an organ that isn't responsive to [cancer-inducing] estrogen, we could reduce breast cancer by 99%," says Dr. Norton, a key researcher in the Evista trials. "And breast cancer isn't the only one. The next one to go is prostate cancer."
Lilly divided its trials into one group of about 7,000 patients and another group of about 12,000. The full results of both clinical trials will be presented at an American Society of Clinical Oncology symposium next month in Los Angeles. The presentation will likely answer some vital questions: Were the ages and general health of the Evista group precisely comparable with those in the control group? How serious and frequent was the one known big side effect of Evista -- a rare form of blood clots?
And only time will answer the biggest question: Does Evista lower cancer risk permanently or simply delay new tumors for a couple of years?
Among its other lethal qualities, experts note, cancer is patient. Says Ms. Pearson of the National Women's Health Network: "I wouldn't trust a drug to reduce breast cancers without 10 years of data."
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