Novel Treatment Combinations With Imlunestrant for Advanced Breast Cancer

By: Vanessa A. Carter, BS
Posted: Tuesday, December 17, 2024

Komal L. Jhaveri, MD, FACP, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, and colleagues evaluated the use of imlunestrant—a next-generation, oral selective estrogen receptor (ER) degrader—alone and in combination with targeted therapy in patients with ER-positive, HER2-negative advanced breast cancer. Their results, published in the Journal of Clinical Oncology, suggest that regardless of the regimen or ESR1 mutation status, imlunestrant demonstrated preliminary antitumor activity with a manageable safety profile in this patient population.

“Taken together, these results show promise for imlunestrant as an oral alternative to fulvestrant and support the ongoing development of imlunestrant in phase III studies as monotherapy or in combination with abemaciclib for endocrine therapy–pretreated patients with advanced breast cancer and as adjuvant monotherapy for early-stage breast cancer,” the authors concluded.

The phase Ia/Ib EMBER study enrolled 262 patients with ER-positive, HER2-negative advanced breast cancer. An interval 3+3 dose-escalation design was implemented, followed by imlunestrant dose expansions as once-daily monotherapy or in combination with the CDK4/6 inhibitor abemaciclib with or without an aromatase inhibitor such as alpelisib or everolimus.

A total of 74 and 188 participants were assigned to phase Ia and Ib, respectively. No discontinuations or dose-limiting toxicities occurred among patients on monotherapy. Grade 1 to 2 fatigue, nausea, and diarrhea were the most commonly reported adverse events at the recommended phase II dose of 400 mg; these patients underwent various modes of prior therapy and achieved a median progression-free survival of 7.2 months.

Individuals who received imlunestrant with abemaciclib plus everolimus (n = 42) or alpelisib (n = 21) did not exhibit any interactions or new safety signals. The median progression-free survival was not reached among patients on the triplet combination, compared with 19.2 months with imlunestrant plus abemaciclib. Of note, those who received imlunestrant plus everolimus had longer median progression-free survival than patients given alpelisib (15.9 vs 9.2 months).

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

Journal of Clinical Oncology

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