Imlunestrant with or without Abemaciclib in Advanced Breast Cancer: Updated Efficacy Results from the phase 3 EMBER-3 trial
Mené sur 874 patientes atteintes d'un cancer du sein ER+ HER2- de stade avancé (durée médiane de suivi : 28,5 mois), cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'imlunestrant avec ou sans abémaciclib
BACKGROUND: At the primary progression-free (PFS) analysis, the phase 3 EMBER-3 trial in endocrine pretreated patients with ER+, HER2- advanced breast cancer (ABC) demonstrated significant PFS benefit with imlunestrant vs. standard of care (SOC: fulvestrant or exemestane) in patients with ESR1 mutations (ESR1m) and with imlunestrant-abemaciclib vs. imlunestrant in all patients, regardless of ESR1m. Herein, we report updated efficacy from a prespecified interim overall survival (OS) analysis.
METHODS: Patients with ER+, HER2- ABC previously treated with aromatase inhibitors ± CDK4/6 inhibitors were randomized (1:1:1) to imlunestrant, SOC, and imlunestrant-abemaciclib. Primary endpoints were PFS in imlunestrant vs. SOC in patients with ESR1m and all patients, and vs. imlunestrant-abemaciclib in all concurrently randomized patients. OS was a key secondary endpoint (tested if the corresponding PFS was statistically significant). Due to only 2 of 3 PFS endpoints being met, a limited significance level was passed to the OS comparisons. Exploratory endpoints included time to chemotherapy (TTC), Chemotherapy-Free Survival (CFS), and PFS2.
RESULTS: A total of 874 patients were randomized (imlunestrant, n=331; SOC, n=330; imlunestrant-abemaciclib, n=213). Median follow-up was 28.5 months, 10.1% of patients remained on treatment (data cut-off: 18Aug2025).
In patients with ESR1m, median OS (mOS) was 34.5 months for imlunestrant vs. 23.1 months for SOC (HR=0.60; 95% CI 0.43-0.86; p=0.0043, boundary for significance not reached). In all patients regardless of ESR1m, mOS was not reached with imlunestrant-abemaciclib vs. 34.4 months with imlunestrant (HR=0.82, 95% CI 0.59-1.16; p=0.2622). Updated PFS demonstrated sustained benefit. Notably, in all patients regardless of ESR1m, the mPFS of imlunestrant-abemaciclib vs. imlunestrant was 10.9 vs 5.5 months (HR=0.59; 95% CI 0.47-0.74; nominal p<0.0001). All pre-specified exploratory endpoints favored imlunestrant-based regimens. Safety remains consistent with prior reports.
CONCLUSIONS: These findings reinforce the clinical benefit of imlunestrant-based regimens as a potential all-oral, chemotherapy-free treatment option for endocrine-pretreated patients with ER+, HER2-ABC.
Annals of Oncology , résumé, 2025