The phase IA/B EMBER study, published in the Journal of Clinical Oncology, reveals that imlunestrant, a novel oral selective estrogen receptor degrader (SERD), exhibits a manageable safety profile and preliminary antitumor activity in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer. This study suggests imlunestrant could be a viable oral alternative to fulvestrant, addressing limitations related to intramuscular administration and dosing optimization, particularly in obese patients.
Imlunestrant Monotherapy Efficacy
The EMBER trial, a global study involving 262 patients with ER-positive, HER2-negative advanced breast cancer, established the recommended phase II dose of imlunestrant at 400 mg once daily. In the dose-escalation phase, no dose-limiting toxicities were observed among the 114 patients who received single-agent imlunestrant. At the 400 mg dose (n = 51), common adverse events included grade 1 and 2 nausea (39.2%), fatigue (39.2%), and diarrhea (29.4%). Notably, this patient population had extensive prior treatment, including CDK4/6 inhibitors (92.2%), fulvestrant (41.2%), and chemotherapy (29.4%). Despite this, the median progression-free survival (PFS) was 7.2 months.
Combination Therapy Results
The study also evaluated imlunestrant in combination with targeted therapies. When combined with abemaciclib, with (n = 43) and without (n = 42) an aromatase inhibitor, the median progression-free survival was 19.2 months and not reached, respectively. The 18-month progression-free survival rates were 60.7% and an estimated 73.4%, respectively. For patients receiving imlunestrant plus everolimus (n = 42), the median progression-free survival was 15.9 months, while those receiving imlunestrant plus alpelisib (n = 21) had a median progression-free survival of 9.2 months. No new safety signals or interactions with the partnered drugs were observed.
Clinical Implications and Future Directions
According to the investigators, exploratory analysis suggests imlunestrant demonstrates antitumor activity regardless of baseline ESR1 mutation status. These findings support the ongoing development of imlunestrant in phase III studies, both as monotherapy and in combination with abemaciclib, for endocrine therapy-pretreated patients with advanced breast cancer (EMBER-3) and as adjuvant monotherapy for early-stage breast cancer (EMBER-4).
Kathy D. Miller, MD, FASCO, of The Indiana University Melvin and Bren Simon Comprehensive Cancer Center Women’s Clinic, commented that imlunestrant provides an oral option with significant activity in previously treated patients, and ongoing phase III trials will determine its role in our therapeutic armamentarium.
The study was funded by Eli Lilly and Company.
