(114) Vaginal/Vulvar Symptoms with Lasofoxifene versus Fulvestrant in ESR1-mutated, ER+/HER2- Metastatic Breast Cancer Patients
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».