Safety and efficacy of imlunestrant in ER+/HER2- advanced breast cancer

A new phase Ia/Ib study recently published on the Journal of Clinical Oncology shows a manageable safety profile and a promising antitumor activity for imlunestrant as monotherapy or in combination with targeted therapy in ER+/HER2- advanced breast cancer patients.

Imlunestrant is a next-generation oral selective estrogen receptor degrader (SERD) designed to deliver continuous ER target inhibition; this new study was designed as a phaseIa/Ib trial to determine the recommended phase II dose, safety, pharmacokinetics and efficacy of imlunestrant, as monotherapy and in combination with targeted therapy, in ER+/HER2- advanced breast cancer. A total of 262 patients were treated with oral imlunestrant once daily; at the recommended phase II dose of 400 mg, this oral SERD showed a favorable safety profile and no new safety signals or interactions were observed, with mostly low-grade, reversible, gastrointestinal symptoms, suggesting potential suitability for chronic administration. Moreover imlunestrant showed a promising antitumor activity in cyclin-dependent kinase 4/6 inhibitor–pretreated patients as monotherapy and in combination with everolimus/alpelisib. In CDK4/6i-naïve patients, imlunestrant + abemaciclib and imlunestrant + abemaciclib + aromatase inhibitor had a 18-month progression-free survival of 60.7% and 73.4%, respectively. As authors conclude, «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».