Third-Generation SERMs May Face Uphill Battle

Abstract

Lasofoxifene, a third-generation selective estrogen receptor modulator (SERM), has emerged from the phase III PEARL trial with what could be considered flying colors. Compared with placebo, the drug reduced breast cancer risk in postmenopausal women with osteoporosis as effectively as firstgeneration tamoxifen and second-generation raloxifene, prevented more kinds of fractures than raloxifene, and did not raise the risk of endometrial cancer like tamoxifen. As reported in this issue of the Journal, lasofoxifene was particularly effective in reducing risk in higherrisk women and those with high estradiol levels. But don’t look for lasofoxifene as an immediate option in breast cancer chemoprevention. The drug, made by Pfi zer, has approval in Europe, but only as an osteoporosis treatment. In the U.S., the company has withdrawn its application to the Food and Drug Administration despite the PEARL trial results. According to its most recent fi ling with the Securities and Exchange Commission, in August, Pfi zer is now “exploring strategic options for [lasofoxifene], including but not limited to out-licensing or sale.”