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Lasofoxifene cuts fractures, breast CA, ischemic events — but still has a down side

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – In postmenopausal women with osteoporosis, the selective estrogen-receptor modulator lasofoxifene cuts the risks of fractures, estrogen-receptor-positive breast cancer, coronary disease, and stroke, the international PEARL study shows.

As do estrogen and other selective estrogen-receptor modulators, however, lasofoxifene increased the risk of venous thromboembolic events.

The findings, reported in The New England Journal of Medicine for February 25, stem from a randomized study of 8556 women who received either once-daily lasofoxifene (0.25 or 0.5 mg) or placebo for 5 years. All had bone mineral density T scores of -2.5 or less at the spine or femoral neck, lead author Dr. Steven R. Cummings, from the University of California, San Francisco, and colleagues note.

Compared with placebo, the higher dose of lasofoxifene reduced the risks of vertebral fracture (HR, 0.58), nonvertebral fracture (HR, 0.76), ER-positive breast cancer (HR, 0.19), coronary heart disease events (HR, 0.68), and stroke (HR, 0.64). The lower dose cut the risks of vertebral fracture (HR, 0.69) and stroke (HR, 0.61).

Both doses of lasofoxifene more than doubled the risk of venous thromboembolic events, the report indicates.

Two lower-dose lasofoxifene patients, two higher-dose lasofoxifene patients, and three patients given placebo developed endometrial cancer.

Mortality rates per 1000 person-years were 7.0 with lower-dose lasofoxifene, 5.7 with higher-dose lasofoxifene, and 5.1 with placebo, the report indicates.

Lasofoxifene is currently under review by the U.S. Food and Drug Administration as a treatment for postmenopausal osteoporosis in at-risk women. But while the current findings suggest that lasofoxifene is superior to placebo in many respects, the new drug may be no better than other selective estrogen-receptor modulators already on the market, according to an editorial.

“Given the plethora of drugs currently available for osteoporosis, studies of new agents should show clear benefits over existing agents,” Dr. Carolyn Becker, from Brigham and Women’s Hospital, Boston, writes.

But, she says, “On the basis of this criterion, the results of the PEARL trial suggest that lasofoxifene offers no major clinically important benefits over raloxifene for the skeleton, breast, heart, or reproductive tract.”

PEARL was funded by Pfizer, the developer of lasofoxifene.


N Engl J Med 2010;362:686-696,752-754.