101 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

Background

In EMBER-3, patients with estrogen receptor–positive (ER+), HER2-negative (HER2–) advanced breast cancer with disease progression on or after aromatase inhibitor-based therapy, achieved significant progression-free survival (PFS) improvement with imlunestrant vs standard therapy (SOC: fulvestrant/exemestane) in patients with ESR1 mutations, and with imlunestrant plus abemaciclib vs imlunestrant in all patients, regardless of ESR1 mutation. Exploratory patient-reported outcomes (PRO) analyses are presented here.

Methods

EORTC QLQ-C30 was administered at baseline and every 8 weeks until treatment discontinuation, with a longitudinal mixed model for repeated measures used to calculate mean change difference (MCD) from baseline. A 10-point change or difference was defined as clinically meaningful. PRO-CTCAE (diarrhea frequency) was administered weekly (0[never]-4[almost constantly]). PRO-CTCAE (injection site reaction [ISR]) was administered to fulvestrant recipients weekly for 2 weeks post- injection (yes/no [pain/swelling/redness]).

Results

In patients with ESR1 mutations, EORTC QLQ-C30 scores were generally maintained, with treatment differences favoring imlunestrant vs SOC. Patients with ESR1 mutations on imlunestrant had improved global health status (GHS)/QOL and physical function (PF) scores from baseline, while scores with SOC declined (MCD between treatments: 7.4 [1.3, 13.6]; 4.0 [–0.7, 8.7]). In the overall population, GHS/QOL and functional scores were generally maintained, with treatment differences favoring imlunestrant vs SOC vs imlunestrant plus abemaciclib. Most fulvestrant recipients (72%) reported ISR at any time while on treatment, with 47% reporting ISR at the majority of their assessments. Patients reported similarly low rates of “frequent” or “almost constant” diarrhea with imlunestrant (3%) and SOC (2%) and higher rates with imlunestrant plus abemaciclib (22%).

Conclusions

GHS/QOL and PF were maintained across treatment arms in the EMBER-3 trial, despite the increased frequency of diarrhea in the imlunestrant plus abemaciclib arm. The importance of ISR as a clinically relevant adverse effect is demonstrated by the high incidence of patient-reported ISR with fulvestrant. These results support the efficacy and safety of imlunestrant as monotherapy or combined with abemaciclib as an all-oral targeted therapy option.

Previously presented at American Society of Clinical Oncology - 61st Annual Meeting