Androgen receptor agonism in advanced oestrogen receptor-positive breast cancer
Mené sur 136 patientes atteintes d'un cancer du sein ER+ HER2- AR+ (âges médians : 60,5 et 62,5 ans ; durée médiane de suivi : 7,5 mois), cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de bénéfice clinique en semaine 24, et la toxicité de l'énobosarm (un modulateur sélectif des récepteurs aux androgènes non stéroïdiens)
The androgen receptor is expressed in a majority of oestrogen receptor-positive breast cancers, acting as both a promoter and inhibitor of tumour cell growth under various conditions of oestrogen stimulation. 1 When oestrogen receptors are activated, androgen receptors act as a competitive binder, decreasing downstream oestrogen receptor activity. However, in the setting of treatment with endocrine therapy, androgen receptors can act as an accessory growth pathway to bypass oestrogen receptor blockade. 1 In an attempt to address resistance to endocrine therapy, androgen receptor antagonists have been investigated in combination with endocrine therapy in advanced oestrogen receptor-positive breast cancer, but have not enhanced the efficacy of endocrine therapy. Neither a randomised phase 2 study of adding enzalutamide (an androgen receptor inhibitor) to exemestane, 2 nor a randomised phase 2 study of abiraterone 3 —with or without a nonsteroidal aromatase inhibitor—showed an improvement in progression-free survival in oestrogen receptor-positive, androgen receptor-positive, and HER2-negative advanced breast cancer with the combination versus endocrine therapy alone.
The Lancet Oncology 2024