Dr Jhaveri on the FDA Approval of Imlunestrant for ESR1+ Breast Cancer

“It’s exciting to see another oral SERD, in this case, imlunestrant, that just got FDA approved on September 25, 2025. [This is] hot off the press and exciting for our patients. It’s good to have options.”

Komal Jhaveri, MD, FACP, section head of the Endocrine Therapy Research Program, clinical director of the Early Drug Development Service, and the Patricia and James Cayne Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center, discussed the clinical significance of the FDA approval of imlunestrant (Inluriyo) for patients with pretreated, ESR1-mutated advanced or metastatic breast cancer.

On September 25, 2025, the FDA approved imlunestrant for the treatment of adult patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer harboring ESR1 mutations whose disease has progressed after at least 1 prior line of endocrine therapy. This regulatory decision was backed by data from the phase 3 EMBER-3 trial (NCT04975308).

This approval provides a crucial additional treatment option alongside elacestrant for the management of ESR1-mutant ER-positive, HER2-negative metastatic breast cancer, Jhaveri began.Although the current indications for each of these oral selective estrogen receptor degraders (SERDs) are similar for ESR1-mutant tumors, there are slight distinctions between the toxicity profiles of these agents, she said. Imlunestrant is generally associated with low-grade diarrhea and fatigue, and its package insert does not require mandatory lipid monitoring, she explained. In contrast, elacestrant was reported to cause slightly more nausea, and use of this agent mandates lipid monitoring at baseline and periodically throughout therapy, she added. Both drugs are otherwise well tolerated, with low discontinuation rates, she emphasized.

Although imlunestrant is currently approved only as monotherapy in the metastatic setting, a highly attractive subset of EMBER-3 data supports its use in combination with abemaciclib (Verzenio), according to Jhaveri. The efficacy of this combination was particularly striking for the patients who had already progressed on a CDK4/6 inhibitor, she continued. Unlike the imlunestrant monotherapy data, the doublet data proved effective even in patients with ESR1 wild-type disease, she noted.

A unique characteristic of imlunestrant is that it is a brain-penetrant oral SERD, Jhaveri reported. A post hoc exploratory analysis of EMBER-3 showed that patients who already had central nervous system (CNS) metastases derived some benefit from the agent, she stated. This feature is also highly relevant for the combination, as abemaciclib also exhibits CNS activity, suggesting the doublet should be more effective against brain metastasis, Jhaveri explained. She concluded, noting that she hopes to see this combination approved or endorsed by guidelines, as many patients require drug combinations rather than monotherapies.