EMBER-3: Imlunestrant Plus Abemaciclib Improves PFS in ER+ Breast Cancer

Imlunestrant plus abemaciclib showed consistent benefit over imlunestrant alone in patients with estrogen receptor-positive (ER-positive), HER2-negative advanced breast cancer regardless of biomarker status or prior CDK4/6 inhibitor treatment (CDK4/6i), according to a subgroup analysis from the EMBER-3 clinical trial.

The combination significantly improved progression-free survival (PFS) over imlunestrant across key clinicogenomic subgroups. Findings were presented by Cristina Saura Manich, MD, PhD, Vall d’Hebron University Hospital, Barcelona, Spain, during the 2025 European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress held in Munich, Germany.

“EMBER-3 is the first phase 3 trial to show benefit of an oral selective estrogen receptor degrader (SERD) plus CDK4/6i after disease progression on prior CDK4/6i,” Saura said.

The phase 3, open-label trial enrolled 874 patients with ER-positive, HER2-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, given alone or with a CDK4/6 inhibitor.

Patients were randomly assigned 1:1:1 to receive imlunestrant, standard of care (SOC) endocrine monotherapy, or imlunestrant plus abemaciclib.

The study’s primary end points were investigator-assessed PFS for imlunestrant compared with SOC in patients with ESR1 mutations, imlunestrant versus SOC endocrine monotherapy in all patients, and imlunestrant plus abemaciclib versus imlunestrant alone in all patients. The subgroup analysis presented at ESMO examined PFS for the combination compared with monotherapy among patients pretreated with CDK4/6i.

Of the 426 patients included in the analysis, the majority (65%) received prior CDK4/6i therapy with palbociclib being the most used. Prior to trial enrollment, 70% of pretreated patients were on CDKJ4/6i therapy for at least 12 months.

More than half (56%) of patients had visceral metastases, 37% had ESR1 mutations, and 40% had PI3K-pathway mutations, including PIK3CA, AKT1, and PTEN.

Results of the study showed a PFS benefit from the combination therapy compared with single agent imlunestrant. The median PFS was 9.1 months versus 3.7 months, respectively. Moreover, this effect was consistent across multiple clinicogenomic subgroups, including ESR1 and PI3K-pathway mutations. The survival benefit was observed regardless of the duration or type of CDK4/6i received by patients during previous treatment, Dr. Saura said.

Previous research published in the New England Journal of Medicine showed a PFS of 9.4 months among patients treated with imlunestrant plus abemaciclib versus 5.5 months with imlunestrant alone.

References:

1. Abstract 297O. ESMO Breast Cancer Annual Congress. https://clin.larvol.com/abstract-detail/ESMO-BC%202025/75278122
2. Jhaveri KL, et al. N Engl J Med. 2025 Mar 27;392(12):1189-1202. doi:10.1056/NEJMoa2410858.