EMBER-3 Trial: Imlunestrant Improves PROs in ER+/HER2– Breast Cancer

At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, researchers presented an exploratory patient-reported outcomes (PRO) analysis of the EMBER-3 trial.

Dr. Giuseppe Curigliano, Istituto Europeo di Oncologia, IRCCS, University of Milano, Milano, Italy, and colleagues wrote, “Imlunestrant (imlu) is a next-generation, brain-penetrant, oral selective estrogen receptor degrader. The EMBER-3 trial, in patients with ER+, HER2- ABC who had disease progression on or after aromatase inhibitor-based therapy, showed significant progression-free survival (PFS) improvement with imlu versus standard therapy (SOC, fulvestrant, or exemestane) in patients with ESR1 mutations (ESR1m), and with imlunestrant+abemaciclib (imlu+abema) versus imlu in all patients, regardless of ESR1m.”

The EORTC QLQ-C30 questionnaire, which measures quality of life (QoL) in patients with cancer, was given at baseline (BL) and every 8 weeks until the treatment ended.

A longitudinal mixed model for repeated measures was employed in the prespecified QLQ-C30 analysis to assess the average change from BL in patients with a BL score greater than or equal to 1 post-BL score.

The PRO-CTCAE assessed diarrhea frequency every week, with responses ranging from 0 (never) to 4 (almost constantly).  For recipients of fulvestrant, the PRO-CTCAE regarding injection site reaction (ISR) was administered weekly for two weeks following the injection, utilizing a yes or no format for assessing pain, swelling, and redness. A descriptive analysis was performed on the PRO-CTCAE data.

Results showed that in patients with ESR1m breast cancer, imlu monotherapy led to many improved or stable EORTC QLQ-C30 scores, whereas standard of care (SOC) scores either deteriorated or did not change. Specifically, patients with ESR1m receiving imlu experienced better global health status (GHS)/QoL and physical function (PF) scores, in contrast to the declines seen with SOC (mean change differences between the two treatments were 9.9 [0.1, 19.7] for imlu and 6.2 [-0.8, 13.1] for SOC).

“These PRO findings mirror the PFS findings in this group. In the overall population, GHS/QoL scores declined similarly with imlu versus SOC (mean change differences: 0.5 [-4.7, 5.7]), while PF scores were maintained with imlu versus a slight decline with SOC (mean change difference: 2.5 [-1.1, 6.1]).”, noted the researchers.

The findings indicated that most patients treated with fulvestrant (72%) experienced ISR at some point during their treatment, averaging 31% in the first week of the initial six cycles.

Treatment using imlu+abema compared to imlu resulted in comparable decreases across all patients, with minimal average variances in GHS/QoL and PF scores (0.8 [-7.4, 5.9]; -2.2 [-6.6, 2.2], respectively). Patients experienced comparably low rates of “frequent” or “almost constant” diarrhea with imlu (3%) and standard of care (2%), whereas those on imlu+abema reported a higher incidence of 22%.

Based on their findings, the researchers concluded that PROs from EMBER-3 indicated that patients with ESR1 mutations experienced superior GHS/QOL and PF while on imlu versus SOC, reflecting efficacy outcomes. The researchers also noted that while the incidence of CTCAE-defined ISRs was infrequent, the elevated rate of PRO-CTCAE ISRs highlights that prescribers often overlook this relevant adverse event. Additionally, all patients showed similar GHS/QOL and PF when imlu+abema was compared to imlu alone, and these findings ultimately support the efficacy and safety of imlu relative to the current SOC.