Sermonix Pharmaceuticals' investigational drug lasofoxifene has demonstrated significant improvements in urogenital symptoms among women with ESR1-mutated, ER+/HER2- metastatic breast cancer, according to newly published data from the ELAINE-1 Phase 2 trial.
The secondary endpoint analysis, published in Clinical Breast Cancer, revealed that patients treated with lasofoxifene experienced a 74% decrease in mean composite vaginal and vulvar symptoms by week 16, while those receiving fulvestrant showed a 36% increase in symptoms.
Patient-Reported Outcomes and Symptom Analysis
Among the 103 enrolled patients, 72 participants (70%) completed the vaginal (VAS) and vulvar (VuAS) assessment scales. The study population, with a mean age of 61.5 years, reported significant urogenital symptoms at baseline:
- 40% experienced vaginal dryness
- 25% reported vulvar dryness
- 22% noted vaginal pain
- 26% of patients reported at least one moderate to severe symptom
The analysis identified several factors associated with more severe baseline symptoms, including:
- Age under 40 years
- Absence of visceral disease
- Previous adjuvant tamoxifen use
- Extended duration of aromatase inhibitor treatment
Clinical Efficacy Context
These quality-of-life improvements complement previously reported efficacy data from ELAINE-1, where lasofoxifene showed promising results compared to fulvestrant:
- Median progression-free survival: 5.6 vs 3.7 months (HR 0.669; 95% CI, 0.434-1.125)
- Objective response rate: 13.2% vs 2.9%
- Clinical benefit rate: 36.5% vs 21.6%
"Recent progress in breast cancer management is leading to improved patient outcomes and longevity," said Dr. David Portman, Sermonix founder and chief executive officer. "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."
Future Research Direction
The ongoing Phase 3 ELAINE-3 trial (NCT05696626) will further investigate lasofoxifene's potential benefits. This registrational study compares lasofoxifene plus abemaciclib to fulvestrant plus abemaciclib and incorporates the FACT B-Endocrine Symptoms scale to evaluate impacts on various quality-of-life domains, including:
- Vaginal dryness
- Painful intercourse
- Sexual interest
- Other quality-of-life measures
Lasofoxifene's unique tissue selectivity and demonstrated anti-tumor activity, both as monotherapy and in combination with CDK4/6 inhibitors, position it as a promising therapeutic option for patients with ESR1-mutated breast cancer, particularly those who have developed endocrine resistance.
