New York Times | June 4, 2011
A drug now used to prevent recurrences of breast cancer can also reduce the risk of it occurring in the first place, providing a new option for women at high risk of getting the disease, researchers reported here on Saturday.
Two drugs, tamoxifen and raloxifene, are already approved to prevent breast cancer but both are rarely used for that purpose, in part because they can have serious side effects like blood clots. The researchers said the new option, exemestane, does not have those side effects and might be more acceptable.
“There’s a very safe therapy that looks highly effective in preventing breast cancer,” Dr. Paul E. Goss, professor of medicine at Harvard and Massachusetts General Hospital, said at a news conference at the annual meeting of the American Society of Clinical Oncology. He was the lead investigator in the study, which was presented at the conference and published online by the New England Journal of Medicine.
Exemestane, also known by the brand name Aromasin, is one of a class of compounds known as aromatase inhibitors. These drugs stop the production of estrogen, which fuels tumor growth. They have proven superior to tamoxifen in preventing recurrence of cancer after a breast tumor is removed.
So researchers have long suspected that aromatase inhibitors would also reduce the risk of an initial occurrence of breast cancer, though this is the first big randomized study to demonstrate that.
The trial involved 4,560 post-menopausal women in the United States, Canada, France and Spain who were considered to be at a higher than normal risk of developing breast cancer either because of being over at least 60 or other factors. After a follow-up of about three years, 11 women getting the drug had developed invasive breast cancer compared with 32 of the women receiving a placebo. That is a reduction in risk of 65 percent.
But in absolute terms, 1.4 percent of women in the placebo group developed cancer compared with about one-half of 1 percent of women taking the drug.
About 94 women would have to be treated for three years to prevent one case of breast cancer, Dr. Goss said. In the trial, exemestane side effects were acceptable, he said. But women who took exemestane had more hot flashes and arthritis than those who had the placebo.
Still, whether exemestane will catch on where the other drugs have not remains to be seen.
Some doctors and patient advocates said that aromatase inhibitors had known side effects like bone pain and joint pain that caused many women who already had had cancer to stop taking them. For healthy women, that would be an even harder sell.
“People are going to think very, very hard about it before they are going to take an aromatase inhibitor in this setting,” said Dr. Eric Winer, a breast cancer specialist at the Dana-Farber Cancer Institute in Boston. He noted the study was not designed to show whether women who took exemestane lived longer.
Diana Zuckerman, president of the Cancer Prevention and Treatment Fund, a patient education group, said that the results were promising but that women in the study were followed for only three years, too short a period to judge long-term effects from taking the drug.
Dr. J. Leonard Lichtenfeld, deputy medical director of the American Cancer Society, said the drugs would be more accepted if there were a way to better predict who was truly at risk of getting breast cancer.
Another factor working against broad use is that aromatase inhibitors are now prescribed by oncologists. But for prevention, “They would have to be prescribed by gynecologists and family doctors,” said Dr. George W. Sledge Jr., a breast cancer specialist at Indiana University. “These doctors are not comfortable with these drugs.”
Patent protection on the drug expired in April. Generic versions will mean lower prices.
But generic competition also means that Pfizer, which sells Aromasin, has little incentive to seek regulatory approval for the drug for preventing breast cancer. The drug could still be available to women off label, but insurers might be reluctant to pay.
Pfizer declined to comment on whether it would seek such approval. Pfizer helped pay for the study, and Dr. Goss has received honorariums from the company.
Two other studies presented at the conference show that the widely used cancer drug Avastin is effective in delaying the progression of ovarian cancer. But both studies so far have narrowly missed showing that the drug can prolong lives, the ultimate test of a cancer drug. That threatens to embroil the use of Avastin for ovarian cancer in a debate similar to the one surrounding its use in breast cancer.
The drug’s manufacturer, Roche, has filed for approval in Europe to market the drug as a treatment for ovarian cancer. But its American subsidiary, Genentech, is still in discussions with the Food and Drug Administration about whether there is enough evidence for an approval. One question is whether it will be necessary to show that the drug prolongs lives, said Dr. Sandra Horning, who runs cancer clinical trials for Genentech. The F.D.A. is now moving to revoke the approval of Avastin for use in treating breast cancer in part because the drug has not prolonged lives in clinical trials. The F.D.A. will hold a hearing on this issue soon.
One study presented here involved 484 women whose ovarian cancer had recurred after an initial drug treatment. All received two standard drugs, and half of them also received Avastin.
The median time that women lived before their cancer worsened was 12.4 months for those who got Avastin compared with 8.4 months for those who received only the two other drugs.
After two years, more women given Avastin were alive, but the difference was not quite statistically significant. Too few women had died to draw conclusions.
“It really is not appropriate statistically to say we really know anything about overall survival here,” said Dr. Carol Aghajanian of the Memorial Sloan-Kettering Cancer Center, the lead investigator. The trial was sponsored by Genentech.
The other trial, partly paid for by Roche, involved adding Avastin to the standard drugs used as initial therapy. There were 178 deaths in the Avastin arm and 200 among those who got the standard drugs, a finding that narrowly missed statistical significance. However, in a subset of patients considered to be at higher risk of recurrence, there was a statistically significant improvement in survival.