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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Wednesday, February 12, 2025
The next-generation oral selective estrogen receptor degrader (SERD) imlunestrant significantly improved progression-free survival vs standard-of-care endocrine therapy in endocrine therapy–pretreated patients with estrogen receptor–positive, HER2-negative advanced breast cancer and an ESR1 mutation, according to Komal Jhaveri, MD, FACP, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Presented at the 2024 San Antonio Breast Cancer Symposium (SABCS; Abstract GS1-01) and simultaneously published in The New England Journal of Medicine, their findings from the phase III EMBER-3 trial also demonstrated a benefit with the addition of the CDK4/6 inhibitor abemaciclib to imlunestrant monotherapy, regardless of ESR1 mutation status.
Patients were randomly assigned to receive single-agent imlunestrant (n = 331), standard-of-care endocrine therapy (fulvestrant or exemestane; n = 330), or imlunestrant plus abemaciclib (n = 213). A total of 138 and 118 of those who underwent imlunestrant monotherapy and standard-of-care endocrine therapy, respectively, had an ESR1 mutation.
In patients with ESR1-mutated disease, the median progression-free survival was found to be significantly longer with imlunestrant monotherapy vs standard-of-care endocrine therapy (hazard ratio [HR] = 0.62; 5.5 vs 3.8 months). Single-agent imlunestrant was not found to significantly improve progression-free survival in the overall population (n = 661; HR = 0.87). The addition of abemaciclib to imlunestrant monotherapy appeared to significantly prolong the median duration of progression-free survival in all patients (n = 426; HR = 0.57; 9.4 vs 5.5 months), with benefit observed regardless of ESR1 or PI3K pathway mutation status and in the CDK4/6 inhibitor–pretreated population.
The most frequently reported treatment-emergent adverse events with single-agent imlunestrant were fatigue, diarrhea, and nausea. Common treatment-related adverse events with imlunestrant plus abemaciclib included diarrhea (86%), nausea (49%), and neutropenia (48%). Treatment-emergent adverse events of grade 3 or higher were documented in 17%, 21%, and 49% of patients who received single-agent imlunestrant, standard-of-care endocrine therapy, and imlunestrant plus abemaciclib, respectively.
Disclosure: For full disclosures of the study authors, visit sabcs.org.
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