Lasofoxifene
Hormonal / PCTAlso known as: Fablyn, CP-336156, Lasofoxifene Tartrate
Mechanism
Lasofoxifene is a third-generation SERM approved by the European Medicines Agency for osteoporosis. It shows broad tissue selectivity — bone protection, breast cancer risk reduction, cardiovascular benefit, and vaginal health improvement — with minimal uterine stimulation. It is also being investigated for ESR1-mutant ER+ breast cancer.
Technical detail
Lasofoxifene is a naphthalene-derived third-generation SERM with high oral bioavailability and a long half-life (~6 days). The PEARL trial (n=8,556) demonstrated significant reductions in vertebral and non-vertebral fractures, ER-positive breast cancer incidence (79% reduction), coronary heart disease events, and stroke, alongside improvements in vaginal atrophy measures — representing the broadest benefit profile of any SERM. It is currently under investigation (ELAINE trials) for ESR1-mutated advanced ER+ breast cancer, where ESR1 mutations confer resistance to aromatase inhibitors.
Evidence
- strong
Goetz MP et al. (2023) — Ann Oncol — PMID: 38072514
Randomized phase 2 ELAINE 1 trial (NCT03781063) in ESR1-mutated ER+/HER2- metastatic breast cancer showed lasofoxifene produced numerically longer median PFS than fulvestrant (24.2 vs 16.2 weeks; HR 0.699) with acceptable tolerability, supporting clinically relevant anti-estrogen activity.
- strong
LaCroix AZ et al. (2010) — J Natl Cancer Inst — PMID: 21051656
Large randomized PEARL trial in 8,556 postmenopausal women reported lasofoxifene reduced ER-positive breast cancer risk over 5 years while also being studied for fracture outcomes, making it a strong long-horizon human efficacy and risk-reduction citation.