Expanding Oral Therapy Options for ER+ Advanced Breast Cancer

The development of new oral selective estrogen-receptor degraders (SERDs) has increased the treatment options for metastatic ER+/HER2− breast cancer. Imlunestrant is a brain-penetrant SERD shown to have clinical activity in endocrine-refractory tumors, including those that develop ESR1 mutations. It is not yet FDA approved.

In the industry-sponsored, open-label, phase 3 EMBER-3 trial, 874 patients with ER+/HER2− metastatic breast cancer were randomized to standard of care endocrine therapy (SOC; fulvestrant or exemestane), imlunestrant monotherapy, or imlunestrant plus abemaciclib. Eligible patients had disease progression during or within 12 months after neoadjuvant or adjuvant treatment with an aromatase inhibitor (with or without a CDK4/6 inhibitor), or while receiving first-line treatment.

The median progression-free survival (PFS) was longer with imlunestrant monotherapy than with SOC among patients with ESR1 mutations (5.5 vs. 3.8 months; P<0.001) but not among the overall population (5.6 and 5.5 months, respectively; NS). The median PFS with imlunestrant–abemaciclib was longer than with imlunestrant monotherapy (9.4 vs. 5.5 months; P<0.001); the improvement with combination therapy was observed whether or not ESR1 mutation was present. Overall survival was immature.

Grade 3 or higher toxicities occurred in roughly 20% of patients in the imlunestrant monotherapy and SOC groups, compared with almost 50% of those receiving combination therapy.