Imlunestrant Plus Abemaciclib for HR-Positive, HER2-Negative Advanced Breast Cancer: EMBER-3 Trial
According to updated results from the EMBER-3 trial, imlunestrant, as monotherapy or combined with abemaciclib, demonstrates clinically meaningful efficacy and manageable safety among previously treated patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, including those with ESR1-mutated disease.
These findings were presented by Komal Jhaveri, MD, Memorial Sloan Kettering Cancer Center, New York, New York, at the 2025 San Antonio Breast Cancer Symposium in San Antonio, Texas.
In this study, 874 patients who received an aromatase inhibitor with or without a CDK4/6 inhibitor were randomized 1:1:1 to receive imlunestrant alone (n = 331) or in combination with abemaciclib (n = 213) or standard endocrine therapy (n = 330). The primary end point was progression-free survival (PFS) for imlunestrant versus standard endocrine therapy in patients with ESR1 mutations (n = 256) and in the overall population. A key secondary end point of the study was overall survival (OS). Exploratory end points included time to chemotherapy initiation and PFS2.
At a median follow-up of 28.5 months, 10.1% of patients remained on study treatment, including 10% in the imlunestrant arm, 5% in the endocrine therapy arm, and 18% in the imlunestrant plus abemaciclib arm. Median PFS was 5.5 months in the imlunestrant arm, 3.9 months in the endocrine therapy arm, and 10.9 months in the imlunestrant plus abemaciclib arm (P < .0001). Median OS was 34.4 months in the imlunestrant arm, 32.3 months in the endocrine therapy arm, and was not reached in the imlunestrant plus abemaciclib arm (P = .2622). Time to chemotherapy initiation was 15.1 months, 15.5 months, and 27.8 months, while the median PFS2 was 16.7 months, 18.5 months, and 22.6 months, respectively.
In patients with ESR1 mutations, median PFS was 5.5 months in the imlunestrant arm and 3.8 months in the endocrine therapy arm (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47 to 0.82; P = .0007). Median OS was 34.5 months and 23.1 months, respectively (HR, 0.60; 95% CI, 0.43 to 0.86; P = .0043). Time to chemotherapy initiation was 15.6 months in the imlunestrant arm and 10.2 months in the endocrine therapy arm, and median PFS2 was 19.2 months and 13.5 months, respectively.
“Taken together, these updated data reinforce the potential of [imluenstrant] as monotherapy or in combination with [abemaciclib],as an all-oral chemotherapy-free targeted therapy option,” concluded Dr Jhaveri et al.
Source:
Jhaveri KL, Neven P, Casalnuovo M, et al. Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): Updated efficacy results from the phase 3 EMBER-3 trial. Presented at SABCS 2025. December 9 - 12, 2025. San Antonio, Texas. Abstract GS3-08
