89 Imlunestrant With or Without Abemaciclib as First- and Second-Line Therapy in Advanced Breast Cancer (ABC): A Subgroup Analysis From the EMBER-3 Trial

Background

Imlunestrant is a next-generation, brain-penetrant, oral SERD. The EMBER-3 trial in patients with estrogen receptor–positive (ER+)/HER2-negative (HER2–) advanced breast cancer and disease progression on/after an aromatase inhibitor (AI) therapy with or without CDK4/6 inhibitor (CDK4/6i) showed significant progression-free survival (PFS) improvement with imlunestrant over standard therapy (SOC) among patients with ESR1 mutations, as well as with imlunestrant plus abemaciclib over imlunestrant in all patients regardless of ESR1 mutation status. An exploratory analysis of efficacy by line of therapy is presented here.

Methods

Subgroup analyses of PFS were performed by line of therapy for imlunestrant (400 mg once daily) vs SOC (fulvestrant or exemestane per label) in patients with ESR1 mutation and imlunestrant (400 mg once daily) plus abemaciclib (150 mg twice daily) vs imlunestrant and vs SOC in all concurrently randomized patients. Eligible patients included first-line patients with advanced breast cancer who experienced recurrence on/within 12 months from completion of AI with or without CDK4/6i as (neo)adjuvant treatment, and second-line patients who progressed on first-line treatment for advanced breast cancer.

Results

Overall, 33% of patients received study therapy as first-line treatment for advanced breast cancer, while 67% received it as second-line.Among patients with ESR1 mutation across imlunestrant and SOC arms, 21%were treated in the first-line setting and 79% in the second-line setting.Baseline characteristics and demographics were generally balanced. Among all patients, ESR1 mutation were less frequent in the first-line than second-line (24% vs 43%), as were incidences of prior CDK4/6i treatment (12% vs 83%). Consistent PFS benefit was observed for imlunestrant vs SOC in patients with ESR1 mutation, and imlunestrant plus abemaciclib vs imlunestrant and vs SOC in all patients, regardless of line of treatment. A numerically longer PFS was observed in first-line patients (Table).

Conclusions

Consistent with the primary EMBER-3 analyses, a benefit in PFS was observed across the first-line and second-line subgroups. Imlunestrant alone or combined with abemaciclib, provides an all-oral targeted therapy option in the first-line or second-line setting for patients with endocrine therapy-resistant ER+/HER2– advanced breast cancer.