Inluriyo/Verzenio Extends Treatment Benefit in ER+/HER2– Breast Cancer

Among patients with previously treated estrogen receptor–positive (ER-positive), HER2-negative advanced breast cancer, Inluriyo (Imlunestrant), alone or combined with Verzenio (abemaciclib), helped patients stay on treatment longer without their disease worsening, compared with standard endocrine therapy, according to updated results from the EMBER-3 trial.

These data, which were shared at the 2025 San Antonio Breast Cancer Symposium, also showed a trend toward longer overall survival with Inluriyo-based treatments, although this was not statistically significant.

In patients with ESR1 mutations, updated progression-free survival data at a median follow-up of 27.6 months showed that the median progression-free survival in the Inluriyo cohort (138 patients) was 5.5 months versus 3.8 months in the standard-of-care group (118 patients). Among all patients, the median progression-free survival was 10.9 months with Inluriyo plus Verzenio (213 patients) versus 5.5 months with Inluriyo alone (213 patients).

This progression-free survival benefit for the combination was maintained regardless of ESR1 mutation status. Among patients who had previously received a CDK4/6 inhibitor, the median progression-free survival was 9.1 months with Inluriyo plus Verzenio (139 patients) versus 3.7 months with Inluriyo alone (140 patients).

At 50% overall survival maturity, results showed that at a median follow-up of 29.5 months in patients with ESR1 mutations, the median overall survival in the Inluriyo cohort was 34.5 months versus 23.1 months in the standard-of-care group. While not statistically significant, this 11.4-month numerical overall survival benefit was considered clinically meaningful. This overall survival improvement was consistent with Inluriyo across all prespecified subgroups of patients with ESR1 mutations. At 33% overall survival maturity, results showed that at a median follow-up of 27.1 months, the median overall survival was not reached with Inluriyo plus Verzenio versus 34.4 months with Inluriyo alone.

The EMBER-3 update also included data showing a clinically meaningful improvement in time to chemotherapy and progression-free survival 2 with the Inluriyo -based regimens.

In patients with ESR1 mutations, the median time to chemotherapy in the Inluriyo cohort was 15.6 months versus 10.2 months in the standard-of-care group. Among all patients, the median time to chemotherapy was 27.8 months with Inluriyo plus Verzenio versus 15.5 months with Inluriyo alone.

Progression-free survival 2 results in patients with ESR1 mutations showed a median progression-free survival 2 of 19.2 months in the Inluriyo cohort versus 13.5 months in the standard-of-care group. Among all patients, the median progression-free survival 2 was 22.6 months with Inluriyo plus Verzenio versus 18.5 months with Inluriyo alone.

Overall response rates were higher with Inluriyo versus standard-of-care and higher with Inluriyo plus Verzenio versus Inluriyo monotherapy, regardless of ESR1 mutation status.

Safety data were consistent with previously reported outcomes for Inluriyo and Verzenio with no new safety signals.

“Inluriyo, as monotherapy or in combination with Verzenio, provides an all-oral, chemotherapy-free option after progression on endocrine therapy for patients with ER-positive, HER2-negative advanced breast cancer,” said lead study author Dr. Komal Jhaveri, section head of the Endocrine Therapy Research Program, director of the Early Drug Development Service, and the Patricia and James Cayne Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center in New York, New York.

EMBER-3 Trial Design

Between October 2021 and November 2023, the open-label phase 3 EMBER-3 trial enrolled patients with ER-positive, HER2-negative advanced breast cancer previously treated with aromatase inhibitors with or without CDK4/6 inhibitors.

Overall, 874 patients with a median age of 62 were randomized to Inluriyo monotherapy (331 patients), Inluriyo plus Verzenio (213 patients), or standard-of-care (330 patients; investigator’s choice of endocrine therapy: exemestane or fulvestrant). Inluriyo was administered at 400 mg orally once daily and Verzenio was administered at 150 mg orally twice daily. Treatment cycles were 28 days.

At the data cutoff date of August 18, 2025, 10% of patients overall remained on treatment. This included 10%, 5%, and 18% of the single-agent Inluriyo, standard-of-care, and Inluriyo plus Verzenio arms, respectively. When patients discontinued treatment, first subsequent anticancer treatments were similar across the treatment arms.

The primary endpoints were progression-free survival per investigator assessment for single-agent Inluriyo versus standard-of-care in all patients and in patients with ESR1 mutations, as well as progression-free survival for Inluriyo plus Verzenio versus Inluriyo in all patients. Overall survival was a secondary endpoint, and exploratory endpoints included time to chemotherapy and progression-free survival 2.

FDA Approval and Next Steps

Based on the primary progression-free survival analysis of EMBER-3, the FDA approved single-agent Inluriyo in September 2025 for the treatment of patients with ER-positive, HER2-negative, ESR1 mutation-positive advanced breast cancer with disease progression following at least 1 line of endocrine therapy.

Regarding next steps for Inluriyo, Jhaveri said the randomized, open-label, global, multicenter phase 3 EMBER-4 study has completed enrollment, accruing approximately 8,000 patients with ER-positive, HER2-negative early breast cancer who have received 2 to 5 years of adjuvant endocrine therapy with or without a CDK4/6 inhibitor who are at increased risk of recurrence. Patients are being randomized to single-agent Inluriyo or standard-of-care endocrine therapy with an aromatase inhibitor or tamoxifen.

References

1. "Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): Updated efficacy results from the phase 3 EMBER-3 trial," by Dr. Komal Jhaveri, et al. Presented at: San Antonio Breast Cancer Conference; December 9-12, 2025; San Antonio, TX. GS3-08.
2. A study of imlunestrant, investigator’s choice of endocrine therapy, and imlunestrant plus abemaciclib in participants with ER+, HER2– advanced breast cancer (EMBER-3). ClinicalTrials.gov. Updated July 11, 2025. Accessed December 12, 2025. https://clinicaltrials.gov/study/NCT04975308

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