EMBER-3

Arguably one of the most resonating presentations at SABCS 2024 discussed the results of the randomized phase III EMBER-3 trial. This trial evaluates the selective oestrogen receptor degrader (SERD) imlunestrant, alone or in combination with abemaciclib in oestrogen-receptor positive (ER+), HER2-negative advanced breast cancer patients who previously received endocrine therapy (ET). In this video, Prof Patrick Neven, gynaecological oncologist at the University hospitals Leuven and co-author for EMBER-3, discusses the key take home messages from this presentation.

EMBER-3 enrolled a total of 874 patients with ER+/HER2- advanced breast cancer who recurred on or within 12 months of completing their adjuvant therapy with an aromatase inhibitor (AI) with or without a CDK4/6 inhibitor, or who progressed following first line treatment with an AI alone or in combination with a CDK4/6 inhibitor in the advanced setting. Patients were randomly assigned to receive imlunestrant alone, standard of care (SoC) ET (i.e., fulvestrant or exemestane), or a combination of imlunestrant with the CDK4/6 inhibitor abemaciclib.

The median age of patients in the study was 62 years, about 4 out of 10 had an ESR1 mutation and approximately two thirds were previously treated with a CDK4/6 inhibitor. Among patients with an ESR1 mutation, imlunestrant monotherapy resulted in a significantly better progression-free survival (PFS) than SoC ET (median: 5.5 vs. 3.8 months; HR[95%CI]: 0.62[0.46-0.82]; p< 0.001). In contrast, imlunestrant did not improve the PFS compared to SoC ET in the overall study population (median PFS: 5.6 vs. 5.5 months; HR[95%CI]: 0.87[0.72-1.04]; pre-specified critical HR < 0.84).

Interestingly, adding abemaciclib to imlunestrant further improved the PFS of patients. In unselected patients, the imlunestrant-abemaciclib combination resulted in a median PFS of 9.4 months, which was significantly longer than the 5.5 month median PFS seen with imlunestrant alone (HR[95%CI]: 0.57[0.44-0.73]; p< 0.001). This PFS benefit was observed irrespective of the presence of visceral metastases and regardless of the ESR1 or PI3K pathway mutation status. The delay in disease progression obtained with the imlunestrant-abemaciclib combination over imlunestrant alone was particularly pronounced in the subgroup of patients who previously received a CDK4/6 inhibitor, with a median PFS of 9.1 and 3.7 months, respectively (HR[95%CI]: 0.51[0.38-0.68]).

In conclusion, the results of EMBER-3 indicate that imlunestrant, as monotherapy or combined with abemaciclib, represents an effective all-oral targeted therapy option for patients with ER+/HER2- advanced breast cancer who progress on or after ET.