No Significant PFS Benefit With Imlunestrant in Chinese EMBER-3 Cohort

In the Chinese subgroup analysis of the global phase III randomized EMBER-3 trial (NCT04975308), researchers evaluated the oral selective estrogen receptor degrader imlunestrant as monotherapy or in combination with abemaciclib versus standard of care (SOC; fulvestrant or exemestane) in adults with estrogen receptor-positive (ER+), HER2-negative advanced breast cancer previously treated with aromatase inhibitors with or without CDK4/6 inhibitors.

Between November 2022 and April 2025, 83 Chinese patients across 22 centers were randomized (1:1:1) to receive imlunestrant (n = 24), SOC (n = 29), or imlunestrant plus abemaciclib (n = 30). ESR1 mutations were detected in 25% (n = 6), 7% (n = 2), and 20% (n = 6) of patients in each group, respectively. The primary endpoints were investigator-assessed progression-free survival (PFS) comparing imlunestrant with SOC in all patients and in the ESR1-mutated subgroup, as well as imlunestrant-abemaciclib versus imlunestrant in all patients. Secondary endpoints included overall survival and safety, with patient-reported outcomes serving as an exploratory endpoint.

Among patients with an ESR1 mutation, median PFS was 5.5 months for imlunestrant monotherapy versus 2.7 months for SOC (hazard ratio [HR], 0.36; 95% CI, 0.05–2.59). In the same ESR1-mutated population, adding abemaciclib to imlunestrant resulted in a median PFS of 15.7 months compared with 5.5 months for imlunestrant alone (HR, 0.43; 95% CI, 0.11–1.75). When evaluating the total Chinese cohort regardless of mutation status, median PFS was 7.4 months with imlunestrant-abemaciclib versus 5.6 months with imlunestrant monotherapy (HR, 1.04; 95% CI, 0.55–1.98).

Imlunestrant-based regimens were reported to be well tolerated in Chinese patients, with no new safety signals identified relative to the global EMBER-3 population. Patient-reported outcomes were generally maintained, whereas 79% of patients in the fulvestrant arm reported injection-site pain or swelling during treatment. The authors concluded that these findings are generally consistent with global EMBER-3 data and suggest the potential clinical benefit of imlunestrant-based regimens as an oral targeted therapy for Chinese patients with ER+, HER2- advanced breast cancer.

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