Additional findings from the Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE 1) Phase 2 study were presented during the 4th Annual Congress of the International Society of Liquid Biopsy (ISLB) in Miami. Lasofoxifene is an investigational, non-steroidal, selective estrogen receptor modulator (SERM) with benefits on bone health and breast cancer prevention potential.

The bioavailability and activity of lasofoxifene in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. The drug’s novel activity in ESR1 mutations was discovered at Duke University. The investigational drug is being developed by Sermonix Pharmaceuticals.

The initial results from the open-label (NCT03781063) study assessing the efficacy and safety of oral lasofoxifene, versus the current standard of care, intramuscular fulvestrant (Faslodex; AstraZeneca), in postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer (mBC) and an ESR1 mutation were presented on September 10, 2022 during a late-breaking oral presentation at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris, France.

The study results were presented in a poster which explored a potential predictive clinical role of high ESR1 mutation levels. Investigators evaluated mutant allele fraction (MAF) ctDNA dynamics following treatment with lasofoxifene or fulvestrant. The primary endpoint was progression free survival (PFS). Clinical benefit rate (CBR) was also assessed.

“In our analysis of the data from the ELAINE 1 study, lasofoxifene decreased ESR1-mutant expression and efficacy results numerically favored lasofoxifene, independent of baseline MAF,” said Massimo Cristofanilli, M.D., past president of the International Society of Liquid Biopsy (ISLB) and the co-author of the poster presentation.

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“Future, larger trials are necessary to confirm a predictive role of ESR1-mutant MAF in selecting endocrine therapies,” he added.


  • PFS and CBR were 6.04 months and 37% for lasofoxifene versus 4.04 months and 22% for fulvestrant, respectively. Although not statistically significant, all clinical endpoints numerically favored lasofoxifene.

Additional exploratory analyses included in the poster, not-pre-specified:

  • Lasofoxifene decreased MAF in 85% (58/68) of ESR1 variants at 8 weeks from baseline, while fulvestrant decreased MAF in 49% (30/61)
  • With baseline overall MAF ≥2%, lasofoxifene decreased 89% (16/18) and fulvestrant decreased 29% (5/17); with Y537S ≥2%, lasofoxifene decreased 80% (4/5) and fulvestrant decreased 14% (1/7)
  • With a MAF ≥13%, no fulvestrant-treated patients (0/5) achieved a CBR, whereas CBR with lasofoxifene was 38% (3/8)

“The results of our ELAINE 1 study provide very strong rationale for continued development of lasofoxifene for a large subset of breast cancer patients – those with an ESR1 mutation – who are increasingly resistant to endocrine therapies such as aromatase inhibitors, resulting in a poor prognosis,” said David Portman, MD, founder and chief executive officer of Sermonix, and co-author of the poster.

“In this exploratory analysis, lasofoxifene compared to fulvestrant decreased ESR1 mutant ctDNA regardless of baseline MAF. Liquid biopsy ctDNA technology will continue to be used in future lasofoxifene studies to further explore these intriguing findings, and we anticipate further validating the value of ctDNA in a large, Phase 3 registrational study, which we are planning to initiate in the first quarter of 2023.”

Clinical trials
Evaluation of Lasofoxifene Versus Fulvestrant in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation – NCT03781063

Highlights of prescribing information
Fulvestrant (Faslodex; AstraZeneca) [Prescription Information]

[1] Christofanilli, MA. Lasofoxifene Reduced ESR1 Mutant Allele Fraction and Provided Clinical Benefit Versus Fulvestrant in Metastatic Breast Cancer: the ELAINE 1 Trial. Poster 38/ 4th Annual Congress of the International Society of Liquid Biopsy (ISLB).

Featured image: Encouraging mother with breast cancer. 2018-2020 Fotolia/Adobe. Used with permission.

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