A study presented at the San Antonio Breast Cancer Symposium 2025 showed a favorable but nonsignificant improvement in overall survival (OS) for patients with advanced breast cancer and ESR1 mutations treated with imlunestrant. 

Results of the phase 3 EMBER-3 trial also showed a favorable OS trend for patients treated with imlunestrant plus abemaciclib, regardless of ESR1 mutation status. Compared to patients assigned to standard of care, those assigned to imlunestrant-containing regimens continued to demonstrate favorable progression-free survival (PFS), time to chemotherapy, and PFS outcomes. 

The EMBER-3 study compared imlunestrant, an oral estrogen receptor (ER) agonist, to standard fulvestrant or exemestane in previously treated patients with ER-positive, HER2-negative advanced breast cancer. Previously published results showed that single-agent imlunestrant significantly improved PFS in patients with ESR1 mutations, while imlunestrant plus abemaciclib significantly improved PFS regardless of ESR1 mutation status. A third endpoint of PFS with imlunestrant monotherapy in all randomized patients did not reach statistical significance.

“OS was a key secondary endpoint (tested if the corresponding PFS was statistically significant). Due to only 2 of 3 PFS endpoints being met, limited significance level was passed to the OS comparisons.”

─ Komal Jhaveri, MD, FACP, section head, Endocrine Therapy Research Program, and clinical director, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York City

With a median follow-up of 28.5 months, 10% of patients assigned to imlunestrant monotherapy and 18% of patients assigned to imlunestrant plus abemaciclib continued to receive treatment, as did 5% of patients assigned to standard-of-care therapy.

Patients with ESR1 mutations achieved a median OS of 34.5 months with imlunestrant monotherapy compared to 23.1 months with standard-of-care therapy. Despite the positive trend associated with imlunestrant, the P value did not cross the boundary for significance. Median OS for all patients treated with imlunestrant plus abemaciclib was not reached and was 34.4 months for imlunestrant monotherapy, regardless of ESR1 mutation status.

“Updated PFS demonstrated sustained benefit from prior report. Notably, in all [patients] regardless of ESR1 [mutations], the [median PFS] of [imlunestrant plus abemaciclib] vs [imlunestrant] was 10.9 months vs 5.5 months.”

─ Komal Jhaveri, MD, FACP, section head, Endocrine Therapy Research Program, and clinical director, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York City

The median time to chemotherapy was 15.6 months for patients assigned to imlunestrant monotherapy, 27.8 months for patients assigned to imlunestrant plus abemaciclib, and 10.2 months for patients assigned to standard-of-care therapy. The median PFS2 outcomes were 19.2, 22.6, and 13.5 months, respectively.

“Taken together, these updated data reinforce the potential of [imlunestrant], as monotherapy or in combination with [abemaciclib], as an all-oral chemotherapy-free targeted therapy option for [endocrine therapy]-pretreated [patients] with [ER-positive, HER2-negative advanced breast cancer].”

─ Komal Jhaveri, MD, FACP, section head, Endocrine Therapy Research Program, and clinical director, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York City

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By Cameron Kelsall

Reference: https://www.abstractsonline.com/pp8/#!/21392/presentation/2287

Disclosures: Jhaveri declared financial ties to drugmakers. See the abstract for details. EMBER-3 was funded by Eli Lilly and Company.

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