On January 29, 2025 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers (mBC), reported the publication of an article entitled "Effects of Lasofoxifene Versus Fulvestrant on Vaginal and Vulvar Symptoms in Patients with ESR1-Mutated, ER+/HER2-, Metastatic Breast Cancer from the ELAINE-1 Study," in the peer-reviewed journal Clinical Breast Cancer (Press release, Sermonix Pharmaceuticals, JAN 29, 2025, View Source [SID1234649982]).
The previously reported Phase 2 Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE-1) study (NCT03781063) was an open-label, randomized trial evaluating the efficacy and safety of lasofoxifene versus fulvestrant. In the study of women with ESR1-mutant breast cancer who previously had aromatase inhibitor-CDK4/6is, 52 women were randomized to lasofoxifene and 51 to fulvestrant, with progression-free survival (PFS) as the primary endpoint. Lasofoxifene monotherapy had numerically greater PFS (median 5.6 vs 3.7 months; P=0.138; hazard ratio [HR] 0.669 [95% CI, 0.434-1.125]), objective response rate (ORR, 13.2% vs 2.9%; P=0.124), and clinical benefit rate (CBR, 36.5% vs 21.6%; P=0.117) versus fulvestrant. The small sample size of this Phase 2, signal-seeking study limited the statistical power. A favorable safety profile was reported in both treatment groups.1
In this secondary endpoint analysis just published, patients treated with investigational lasofoxifene – but not fulvestrant – demonstrated improved vaginal and vulvar symptoms of dryness and pain as assessed by the validated vaginal and vulvar symptom scale (VAS and VuAS) patient-reported outcome instrument.
"Recent progress in breast cancer management is leading to improved patient outcomes and longevity. Sermonix is highly focused on advancing oral lasofoxifene to hopefully build on that progress and to potentially improve patient quality of life particularly around urogenital health, an issue important to many patients and couples coping with current breast cancer treatments," said Dr. David Portman, Sermonix founder and chief executive officer. "While lasofoxifene has been previously studied in healthy post-menopausal women with urogenital syndrome of menopause, it has not been explored in a population with advanced breast cancer. We are very pleased that Clinical Breast Cancer, a prestigious peer-reviewed journal, recognized the importance of the results from ELAINE-1 and the need for further research in this area."

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Results: Of 103 enrolled patients, 72 (70%) completed the mean vaginal (VAS) and vulvar (VuAS) assessment scales (mean age 61.5 years). Vaginal (40%)/vulvar (25%) dryness and vaginal pain (22%) were the most frequently reported symptoms; 26% reported ≥1 moderate/severe symptom. Lasofoxifene decreased the mean composite VAS/VuAS, VAS, and VuAS from baseline to week 16 by 74%, 74%, and 79%, respectively, while fulvestrant increased them by 36%, 15%, and 63%, respectively. Baseline vaginal/vulvar symptoms were more severe if patients were under age 40, had no visceral disease, used adjuvant tamoxifen previously, or had a longer duration of AI use in the adjuvant/metastatic settings.
The currently enrolling Phase 3, registrational, ELAINE-3 trial (NCT05696626) comparing the efficacy and safety of lasofoxifene plus abemaciclib to fulvestrant plus abemaciclib will incorporate the FACT B-Endocrine Symptoms scale to further explore the potential impact of treatment on vaginal dryness, painful intercourse, sexual interest and other quality-of-life domains.
The open-access Clinical Breast Cancer paper can be accessed online here.
To learn more about Sermonix Pharmaceuticals and lasofoxifene, visit View Source To learn more about the ELAINE studies, visit View Source
Goetz MP et al Annals of Oncology 2023;34:1141-1151

About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc., has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity 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. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy, could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.