This randomized, open-label, phase III trial compared elacestrant, a novel, oral selective ER degrader, vs. standard of care endocrine monotherapy in patients with ER-positive/HER2-negative advanced breast cancer who had one-two lines of endocrine therapy, required pretreatment with a cyclin-dependent kinase 4/6 inhibitor, and ≤ 1 chemotherapy. Elacestrant showed a significant PFS improvement versus SOC both in the overall population and in patients with ESR1 mutations.