(114) Vaginal/Vulvar Symptoms with Lasofoxifene versus Fulvestrant in ESR1-mutated, ER+/HER2- Metastatic Breast Cancer Patients

Abstract

Abstract Introduction Endocrine therapy (ET), specifically aromatase inhibitors (AIs) that lower estrogen to subphysiologic levels and estrogen receptor (ER) degraders that non-selectively and negatively impact ER function, may induce genitourinary syndrome of menopause (GSM) in breast cancer patients. Novel therapies with positive impacts are desirable. Lasofoxifene reduced breast cancer incidence in a large clinical study, while demonstrating ER agonist activity on the urogenital system and bone in clinical trials, including two phase 3 studies in postmenopausal women with moderate to severe vulvovaginal atrophy. Lasofoxifene is currently under investigation as a targeted ET in patients with disease progression on prior ET for metastatic breast cancer (mBC) harboring ER mutations (mESR1). Prevalence of vaginal/vulvar symptoms and potential impact of endocrine treatments on GSM in this patient population are unclear, thus data were gathered from one of the largest studies of lasofoxifene in this patient population to assess its potential positive impact in this area. Objective To investigate changes in vaginal/vulvar symptoms with lasofoxifene versus fulvestrant in women with mESR1, ER+/HER2- mBC in ELAINE 1. Methods Women in the multinational (US, Canada, Israel), phase 2, ELAINE 1 study were randomized to oral lasofoxifene 5 mg (daily) or IM fulvestrant 500 mg (days 1, 15, and 29, then every 28 days), until disease progression/severe toxicity. Vaginal/vulvar symptoms were evaluated as an exploratory endpoint using the vaginal (VAS) and vulvar (VuAS) assessment scales, instruments validated in breast cancer patients to assess dryness, soreness, irritation, and pain using a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). English-speaking patients completed the VAS/VuAS at baseline and every 8 weeks until disease progression. Changes in the mean composite VAS/VuAS score (average of all reported scores for a patient) and the mean score for the most bothersome symptom (the symptom with the greatest baseline score for a patient) over 16 weeks of treatment were analyzed. Results Of 103 enrolled patients, 39/52 (75%) lasofoxifene patients and 33/51 (65%) fulvestrant patients completed the VAS/VuAS; 9/39 (23%) and 10/33 (30%) had ≥1 moderate/severe symptom, respectively (Table). Among those who completed the VAS/VuAS (median age 61.5 years), the mean composite score changed from baseline to week 16 by −74% in lasofoxifene patients versus +36% in fulvestrant patients; the mean score for most bothersome symptom changed by −65% with lasofoxifene and by −5% with fulvestrant. In women with ≥1 moderate/severe symptom at baseline, percent changes from baseline to week 16 in the mean composite VAS/VuAS score were −72% with lasofoxifene versus +32% with fulvestrant. Conclusions In this exploratory analysis in mBC patients unselected for GSM symptoms, lasofoxifene 5 mg/day numerically improved vaginal/vulvar symptoms relative to fulvestrant, albeit with a small sample size. Baseline prevalence of moderate/severe GSM symptoms (20–30%) appears to have been under-reported in this population, which may be due to patients minimizing symptoms less important than mBC disease control or being embarrassed to communicate sexual concerns to their oncologists. Further studies are warranted to evaluate potential clinical benefits of lasofoxifene on GSM symptoms and sexual health in patients with breast cancer. Disclosure Yes, this is sponsored by industry/sponsor: Sermonix Pharmaceuticals. Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Sermonix Pharmaceuticals.