PROs Favor Imlunestrant With/Without Abemaciclib in ER+, HER2– Breast Cancer

In patients with an ESR1 mutation, the median time to deterioration of GHS/QOL with imlunestrant was 5.6 months vs 3.8 months with endocrine therapy.

Imlunestrant, either as monotherapy or combined with abemaciclib (Verzenios), demonstrated benefits in patient-reported outcomes (PROs) as an all-oral targeted therapy for patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer who progressed after endocrine therapy, according to results from the phase 3 EMBER-3 trial (NCT04975308) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

In patients with an ESR1 mutation, based on changes in baseline in the EORTC QLQ-C30 global health status (GHS)/quality of life score (QOL), treatment with imlunestrant was favored compared with standard of care endocrine therapy. At treatment cycle 7, the difference between groups was 9.9 points. The GHS/QOL was typically maintained across both treatment arms.

In patients with an ESR1 mutation, the median time to deterioration of GHS/QOL with imlunestrant was 5.6 months (95% CI, 3.8-11.1), with 53 events, compared with 3.8 months (95% CI, 3.0-6.5) and 50 events, with endocrine therapy (HR, 0.76; 95% CI, 0.51-1.13; P = .15). The investigators noted that estimates were limited by a high rate of censoring.

Additionally, in patients with an ESR1 mutation, overall GHS/QOL and functional domains remained consistent. Imlunestrant was superior regarding the physical, role, social, emotional, and cognitive functional domains. Regarding symptom domains, worse scores were observed with endocrine therapy for fatigue, pain, dyspnea, insomnia, and appetite loss; worse scores were observed with imlunestrant for nausea/vomiting, constipation, and diarrhea. It was noted that symptom domains were broadly similar between treatment groups.

In all patients, the overall changes in GHS/QOL and functional domains were typically maintained across all treatment arms. In order from worst to best, the mean change from baseline for GHS/QOL was imlunestrant plus abemaciclib, endocrine therapy, and imlunestrant; for physical function, social function, emotional function, and cognitive function, it was the same, and for role function, it was endocrine therapy, imlunestrant plus abemaciclib, and imlunestrant.

Regarding symptom domains, imlunestrant plus abemaciclib demonstrated clinically meaningful worse scores regarding nausea/vomiting and diarrhea. The average proportion of time with “frequent” or “almost constant” diarrhea was 22% with imlunestrant plus abemaciclib, 3% with imlunestrant, and 2% with endocrine therapy.

“Consistent with the primary results from EMBER-3, these PRO results reinforce the benefit of imlunestrant, as monotherapy or combined with abemaciclib, as an all-oral targeted therapy option after progression on [endocrine therapy] for patients with ER-positive, HER2-negative [advanced breast cancer],” wrote lead study author Giuseppe Curigliano, MD, PhD, a professor of medical oncology at the University of Milano, and of the European Institute of Oncology, National Institute of Hospitalization and Scientific Care in Milano, Italy, and coauthors, in the presentation.

The trial enrolled approximately 859 patients who were randomly assigned, in a 1:1:1 ratio, to receive either imlunestrant monotherapy (n = 327), imlunestrant plus abemaciclib (n = 208), or endocrine therapy (n = 324). Imlunestrant was given at 400 mg every day in both groups, abemaciclib was given at the labeled dose, and endocrine therapy, which was the investigator’s choice between fulvestrant (Faslodex) or exemestane (Aromasin), was also given at the labeled dose.

Eligible patients had ER-positive, HER2-negative advanced disease. Regarding prior therapies, in the adjuvant setting, patients had recurrence on or within 12 months of completion of an aromatase inhibitor with or without a CDK4/6 inhibitor; for advanced breast cancer, patients had progression on a first-line aromatase inhibitor with or without a CDK4/6 inhibitor and no other therapy for advanced breast cancer.

The trial’s primary end points were investigator-assessed progression-free survival across all treatment groups. Secondary end points included overall survival, blinded independent committee review-assessed PFS, overall response rate, and safety; exploratory end points were PROs.

The PRO measures used and their respective schedules are as follows: the EORTC QLQ-C30 GHS/QOL, function domains, and symptom domains were assessed on day 1 and then every 8 weeks after with short-term follow-up; the EORTC IL-19 physical functioning was assessed every 8 weeks opposite the EORTC QLQ-C30; the PRO-CTCAE diarrhea frequency of diarrhea was assessed on day 1 then every week after with short-term follow-up; and the PRO-CTCAE ISR (injection site reaction) occurrence of IJR was assessed every week of cycle 1 then the first 2 weeks of all other cycles.

It was reported that 72% of patients receiving fulvestrant experienced ISR at any time of treatment; 20% of them had an incidence of less than 25%, 32% had an incidence from 25% to 50%, 30% had an incidence from 50% to 75%, and 17% had an incidence of greater than 75%.

The median investigator-assessed PFS, in all patients, was 9.4 months (95% CI, 7.5-11.9) with imlunestrant plus abemaciclib and 5.5 months (95% CI, 3.8-5.6) with imlunestrant alone (HR, 0.57; 95% CI, 0.44-0.73; P <.001). In patients with an ESR1 mutation, the median PFS was 5.5 months (95% CI, 3.9-7.4) with imlunestrant alone vs 3.8 months (95% CI, 3.7-5.5) with endocrine therapy (HR, 0.62; 95% CI, 0.46-0.82; P <.001).

Regarding safety, treatment-emergent adverse events (TEAEs) of any grade occurred in 83% of patients with imlunestrant, 98% of patients with imlunestrant plus abemaciclib, and 84% of patients with endocrine therapy; of grade 3 or higher, TEAEs occurred in 17%, 49%, and 21%, respectively.

In patients with imlunestrant, dose reductions, treatment discontinuations, and death due to AEs occurred in 2%, 4%, and 2%; in patients with imlunestrant plus abemaciclib, they occurred in 39%, 6%, and 1%, respectively; and in patients with endocrine therapy, they occurred in 0%, 1%, and 1%.

Reference

Curigliano G, O’Shaughnessy J, Bidard FC, 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. J Clin Oncol. 2025;43(suppl_16):1001. doi:10.1200/JCO.2025.43.16_suppl.1001