Patient-Reported Outcomes of Imlunestrant in EMBER-3 Trial for ER-Positive, HER2-Negative Advanced Breast Cancer

The EMBER-3 trial explored patient-reported outcomes (PROs) for imlunestrant, an oral selective estrogen receptor degrader, in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer (ABC) who had progressed after aromatase inhibitor–based therapy. Results showed significant progression-free survival improvement with imlunestrant compared with standard therapy (standard of care [SOC]: fulvestrant or exemestane) in patients with ESR1 mutations (ESR1m), and with imlunestrant plus abemaciclib in all patients regardless of ESR1m status.

PRO analyses using EORTC QLQ-C30 and PRO-CTCAE tools revealed that patients in the ESR1m group treated with imlunestrant monotherapy demonstrated improved or maintained global health status (GHS)/quality-of-life (QOL) and physical function (PF) scores, while patients treated with SOC showed declines. Mean change from baseline favored imlunestrant: GHS/QOL (9.9 points) and PF (6.2 points). Mean differences in overall change from baseline also favored imlunestrant (Table). In the overall population, GHS/QOL scores declined similarly between imlunestrant and SOC (0.5-point difference), while PF scores were maintained with imlunestrant compared with a slight decline with SOC (2.5-point difference).

Injection-site reactions (eg, pain, swelling, redness) were reported by 72% of fulvestrant recipients, emphasizing underappreciation of this adverse event by physicians. Low rates of “frequent” or “almost constant” diarrhea were reported with imlunestrant (3%) and SOC (2%), but higher rates occurred with imlunestrant plus abemaciclib (22%). GHS/QOL and PF scores showed similar declines across all patients, whether treated with imlunestrant plus abemaciclib combination therapy or monotherapy.

In alignment with the efficacy results of EMBER-3, PROs demonstrate that imlunestrant improves GHS/QOL and PF in patients with ESR1m. While injection-site reactions were commonly reported for fulvestrant, they are often overlooked clinically. Imlunestrant, whether as monotherapy or combined with abemaciclib, offers a safe and effective alternative to standard therapies, reinforcing its potential role in treating ER-positive, HER2-negative ABC.

Source: Curigliano G, et al. Patient-reported outcomes (PROs) in patients with ER+, HER2- advanced breast cancer (ABC) treated with imlunestrant, investigator’s choice standard endocrine therapy, or imlunestrant + abemaciclib: results from the phase III EMBER-3 trial. Presented at: 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 1001.