In EMBER-3, patients with ER+, HER2- ABC with disease progression on or after aromatase inhibitor-based therapy, achieved significant PFS improvement with imlunestrant vs standard therapy (SOC: fulvestrant/exemestane) in patients with ESR1 mutations (ESR1m), and with imlunestrant+abemaciclib vs imlunestrant in all patients, regardless of ESR1m. Exploratory PRO analyses are presented here.
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]).
In patients with ESR1m, EORTC QLQ-C30 scores were generally maintained, with treatment differences favoring imlunestrant vs SOC. Patients with ESR1m 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+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+abemaciclib (22%).
GHS/QOL and PF were maintained across treatment arms in the EMBER-3 trial, despite the increased frequency of diarrhea in the imlunestrant+abemaciclib arm. The importance of ISR as a clinically relevant AE 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.