Imlunestrant as Monotherapy or in Combination with Abemaciclib in ER+, HER2− Advanced Breast Cancer: Chinese Subgroup Analysis of the Phase III Randomized EMBER-3 Study

Imlunestrant is a next-generation, oral, selective estrogen receptor degrader. In patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer, the global EMBER-3 study demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) with imlunestrant monotherapy versus standard of care (SOC) fulvestrant or exemestane in patients with an estrogen receptor 1 mutation (ESR1m), and imlunestrant-abemaciclib combination treatment versus imlunestrant monotherapy in all patients, regardless of the ESR1m. We aimed to present data of the Chinese population from the China cohort of the global phase III EMBER-3 study, and the Chinese expansion cohort. Adults (aged ≥ 18 years) with ER+, HER2− advanced breast cancer, and prior treatment with aromatase inhibitors ± cyclin-dependent kinase 4/6 inhibitors, were randomly assigned (1:1:1) to receive imlunestrant, SOC, or imlunestrant-abemaciclib. Primary endpoints were investigator-assessed PFS with imlunestrant versus SOC in all patients and in those harboring an ESR1m, and investigator-assessed PFS with imlunestrant-abemaciclib versus imlunestrant in all patients. Secondary endpoints included overall survival, and safety. Patient-reported outcomes were an exploratory endpoint. Between November 2022 and April 2025, 83 Chinese patients from 22 centers were randomized to imlunestrant (n = 24), SOC (n = 29), or imlunestrant-abemaciclib (n = 30). An ESR1m was detected in 25% (n = 6), 7% (n = 2), and 20% (n = 6) of patients, respectively. In patients with an ESR1m receiving imlunestrant versus SOC, median PFS was 5.5 versus 2.7 months (hazard ratio, 0.36; 95% confidence interval 0.05–2.59). Among patients with an ESR1m receiving imlunestrant-abemaciclib versus imlunestrant, median PFS was 15.7 versus 5.5 months (hazard ratio, 0.43; 95% confidence interval 0.11–1.75); among all Chinese patients receiving these treatments, median PFS was 7.4 versus 5.6 months (hazard ratio, 1.04; 95% confidence interval 0.55–1.98). Imlunestrant-based regimens were well tolerated in Chinese patients, with no new safety signals relative to the global population. Patient-reported outcomes were generally maintained, while the majority (79%) of patients receiving fulvestrant reported injection-site pain or swelling at any time on treatment. Findings from the Chinese population are generally consistent with global EMBER-3 data and suggest the potential clinical benefit of imlunestrant-based therapy as an oral targeted treatment option for Chinese patients with ER+, HER2− advanced breast cancer. ClinicalTrials.gov, NCT04975308 (first posted: 23 July, 2021). Breast cancer that grows in response to the hormone estrogen and that does not have high levels of a protein called human epidermal growth factor receptor 2 (HER2) is the most common type of breast cancer, called estrogen receptor-positive (ER+), HER2− breast cancer. One of the main treatment approaches for this type of breast cancer is hormone therapy (also called endocrine therapy). These medicines either lower the amount of estrogen in the body or stop estrogen from reaching the cancer cells. Hormone therapy is often given with targeted therapies, including cyclin-dependent kinase 4/6 inhibitors, which slow cancer cell growth. However, cancer may stop responding to hormone therapy and start to grow again. One of the main reasons for this is a change (mutation) in a gene called ESR1, which encodes the estrogen receptor protein. Imlunestrant is a medicine that binds to the estrogen receptor, preventing estrogen from binding to it, and breaks down the estrogen receptor. It is approved in the USA, Europe, China, and other countries for patients whose breast cancer has an ESR1 mutation, based on the main results of the phase III EMBER-3 trial. This analysis assessed imlunestrant in Chinese patients from EMBER-3. The results in these patients were generally consistent with the results for the trial as a whole. Imlunestrant, taken on its own or together with a cyclin-dependent kinase 4/6 inhibitor called abemaciclib, may help patients more than standard treatment does and side effects were manageable. Because only a small number of patients from China took part, these findings point to a possible benefit rather than proving one.