Background
The EMBER-3 trial demonstrated a progression-free survival (PFS) benefit for imlunestrant plus abemaciclib vs imlunestrant alone in patients with estrogen receptor–positive (ER+), HER2-negative (HER2–) advanced breast cancer and disease progression on prior aromatase inhibitor therapy alone or with a CDK4/6 inhibitor (CDK4/6i). The MONARCH 2 and postMONARCH trials demonstrated the superiority of fulvestrant plus abemaciclib vs fulvestrant in CDK4/6i-naive and pretreated patients, respectively. The efficacy of imlunestrant plus abemaciclib vs fulvestrant plus abemaciclib has not been directly evaluated. In the absence of head-to-head trial data, indirect treatment comparison (ITC) was leveraged to evaluate treatment efficacy between trials. This study aims to compare efficacy of imlunestrant plus abemaciclib vs fulvestrant plus abemaciclib through an ITC of the EMBER-3, MONARCH 2, and postMONARCH trials.
Methods
To compare investigator-assessed PFS between imlunestrant plus abemaciclib and fulvestrant plus abemaciclib, 3 ITC methods (Bucher method, matching-adjusted indirect comparison [MAIC], and propensity score matching [PSM]), were employed using individual patient-level data from EMBER-3, MONARCH2, and postMONARCH. Bucher is a standard ITC method with MBCC 2026 no population adjustment, while PSM and MAIC are population-adjusted methods. Ten prognostic and predictive factors were selected as baseline covariates. MAIC adjusted the pooled MONARCH 2 and postMONARCH population to match the EMBER-3 population.
Results
Baseline characteristics were generally balanced in the adjusted population by MAIC and PSM. Although not powered for formal hypothesis testing, PFS favored imlunestrant plus abemaciclib vs fulvestrant plus abemaciclib across all 3 ITC methods including Bucher [EMBER-3: effective sample size (ESS) = 426, pooled MONARCH 2/postMONARCH: ESS = 1037 (HR, 0.77; 95% CI, 0.58-1.04)], MAIC [EMBER-3: ESS = 426, pooled MONARCH 2/postMONARCH: ESS = 473 (HR, 0.77; 95% CI, 0.55-1.06)] and PSM [EMBER 3: ESS = 343, pooled MONARCH 2/postMONARCH: ESS = 343 (HR, 0.83; 95% CI, 0.56-1.22)].
Conclusion
In this exploratory ITC analysis, the all-oral targeted therapy imlunestrant plus abemaciclib showed a consistent numerical PFS benefit compared with fulvestrant plus abemaciclib in patients with ER+, HER2– advanced breast cancer previously treated with endocrine therapy with or without CDK4/6i
Previously presented at European Society for Medical Oncology 50th Congress (ESMO 2025)
