Imlunestrant shows efficacy both with and without abemaciclib

Various endocrine therapies and CDK4/6 inhibitors have improved the treatment of ER⁺HER2⁻breast cancer, although resistance remains common and often involves ESR1 (encoding ERα) mutations. Now, data from the phase III EMBER-3 trial demonstrate that the next-generation, brain-penetrant, oral selective ER degrader imlunestrant delays disease progression in previously treated patients with ESR1 mutations, and regardless of ESR1 status when combined with abemaciclib.

In EMBER-3, patients with progression of ER⁺ HER2⁻ breast cancer during or ≤1 year after completing (neo)adjuvant therapy with an aromatase inhibitor, or during first-line treatment for advanced-stage disease, were randomly assigned to receive imlunestrant (n = 331), standard endocrine therapy (exemestane or fulvestrant; n = 330), or imlunestrant–abemaciclib (n = 213). The majority of patients (59.8%) had also received a prior CDK4/6 inhibitor, most for advanced-stage disease. The primary end points were progression-free survival (PFS) with imlunestrant versus standard therapy among patients with ESR1 mutations and among all patients, and with imlunestrant–abemaciclib versus imlunestrant among all patients.