Lasofoxifene Is Potential New Option for Breast Cancer Risk Reduction
An investigational agent in the same family of drugs as tamoxifen and raloxifene may be as or more effective in reducing breast cancer risk in some women, according to the findings of a large clinical trial. The drug, lasofoxifene, also appears to have important benefits for both bone and heart health and, with one exception, appears to lack the rare but potentially serious side effects associated with tamoxifen and raloxifene. The results were published online November 4, 2010, in the Journal of the National Cancer Institute.
The findings come from a randomized clinical trial called PEARL, in which more than 8,500 postmenopausal women with osteoporosis were randomly assigned to take a placebo or one of two different doses of lasofoxifene (0.25 mg or 0.5 mg) daily for 5 years. Initial results, based on 3 years of follow-up, showed a reduced risk of estrogen receptor (ER)-positive breast cancer in women who received the higher dose of lasofoxifene compared with the placebo.
The new, more mature results, which provide 5 years of participant follow-up, show the overall risk of breast cancer was reduced by 79 percent, and the risk of invasive ER-positive breast cancer was reduced by 83 percent in women who took 0.5 mg of lasofoxifene compared with women who took the placebo.
There was some risk reduction seen with the lower dose of lasofoxifene, but it was not statistically significant, reported Andrea LaCroix, Ph.D., of the Fred Hutchinson Cancer Research Center and her colleagues. Women who took the higher lasofoxifene dose also had statistically significant reductions in the risk of vertebral and nonvertebral fractures, cardiac events, and strokes. The only notable side effect was an increased risk of blood clots.
The researchers also conducted a nested case-control study that included all 49 cases of breast cancer in the trial and 156 women from the trial’s placebo arm. Women with higher levels of the hormone estradiol at study entry, they found, seemed to gain a greater cancer prevention benefit from lasofoxifene, but the difference was only statistically significant for total breast cancer incidence, not ER-positive breast cancer.
“We need more complete information about the long-term effects of lasofoxifene on both beneficial and unfavorable outcomes,” cautioned Victor Vogel, M.D., of the Geisinger Medical Center in an accompanying editorial. Although women in the trial were, on average, significantly younger than participants in the STAR trial, which affirmed the breast cancer risk reduction benefits of both tamoxifen and raloxifene, they were also at lower overall risk of breast cancer (based on their Gail model scores).
Nevertheless, given the “dramatic” risk reduction seen with lasofoxifene in the PEARL trial, Dr. Vogel called the findings “encouraging.” Lasofoxifene is still an investigational agent. In May, Pfizer, which manufactures the drug, withdrew its application to the FDA to market the drug for the treatment of osteoporosis. According to a company spokesperson, Pfizer is investigating several options for the drug, including selling it to another company.