The EMBER-3 trial (NCT04975308) demonstrated a progression-free survival (PFS) benefit for imlunestrant plus abemaciclib compared with imlunestrant alone in patients with estrogen receptor (ER)-positive/HER2-negative advanced breast cancer (ABC) who experienced disease progression following prior aromatase inhibitor therapy, either alone or in combination with a cyclin-dependent kinase (CDK)4/6 inhibitor. The MONARCH 2 (NCT02107703) and postMONARCH (NCT05169567) trials established the superiority of fulvestrant plus abemaciclib over fulvestrant alone in CDK4/6 inhibitor−naïve and pretreated patients, respectively. However, no head-to-head trial data exist comparing the efficacy of imlunestrant plus abemaciclib with fulvestrant plus abemaciclib. To address this gap, an indirect treatment comparison (ITC) was conducted using data from the EMBER-3, MONARCH 2, and postMONARCH trials to evaluate the efficacy of these regimens.

Investigator-assessed PFS was compared between imlunestrant plus abemaciclib and fulvestrant plus abemaciclib using 3 ITC methods: the Bucher method, matching-adjusted indirect comparison (MAIC), and propensity score matching (PSM). The Bucher method is a standard ITC technique that does not adjust for differences in patient populations, whereas MAIC and PSM are population-adjusted methods that account for baseline differences. Ten prognostic and predictive factors were selected as covariates for adjustment. MAIC adjusted the pooled MONARCH 2/postMONARCH population to match the EMBER-3 population.

Baseline characteristics were generally balanced in the adjusted populations using MAIC and PSM techniques. Across all 3 ITC methods, PFS consistently favored imlunestrant plus abemaciclib over fulvestrant plus abemaciclib (hazard ratio, 0.77-0.83).

This exploratory ITC analysis suggests that the all-oral targeted therapy imlunestrant plus abemaciclib provides a consistent numerical PFS advantage compared with fulvestrant plus abemaciclib in ER-positive/HER2-negative ABC patients previously treated with endocrine therapy, with or without CDK4/6 inhibitors. These findings highlight the potential of imlunestrant plus abemaciclib as an effective treatment option and warrant further investigation through direct comparative trials.

Source: Bidard FC, Jhaveri KL, Kalinsky KM, et al. Imlunestrant plus abemaciclib versus fulvestrant plus abemaciclib in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC): an indirect treatment comparison (ITC) of three phase 3 trials. Presented at: ESMO Congress 2025. October 20, 2025; Berlin, Germany. Abstract 496P.