A New Endocrine Agent for ER+/HER2− Breast Cancer

Whereas recent approaches to hormone receptor–positive breast cancer have focused on combining endocrine therapy with targeted therapies such as CDK4/6 inhibitors and mTOR inhibitors, development of new endocrine agents has been lacking. Preclinical work has shown that AZD9496 — an oral, nonsteroidal, small-molecule, selective antagonist and degrader of estrogen receptor (ER) α — decreases expression of the progesterone receptor in models with ESR1 mutations and causes tumor regression in animal models.

Now, investigators have conducted an industry-sponsored, first-in-human, phase I, dose-escalation, dose-expansion study to test the safety and efficacy of AZD9496 (20 mg 4 times daily, escalated to 600 mg twice daily) in 45 patients with adva…