Imlunestrant significantly improves PFS for patients with advanced breast cancer
Mené sur 874 patientes atteintes d'un cancer du sein ER+ HER2- de stade avancé, cet essai multicentrique de phase III évalue l'efficacité, du point de vue de la survie sans progression, de l'imlunestrant, avec ou sans abémaciclib, après l'échec d'inhibiteurs de CDK4/6
Imlunestrant conferred significantly longer progression-free survival (PFS) than standard therapy to patients with advanced breast cancer with ESR1 mutations. When combined with abemaciclib, imlunestrant improved PFS in all patients regardless of their ESR1 mutation status, according to the primary analysis of the EMBER-3 trial study published in The New England Journal of Medicine.1
Imlunestrant is a next-generation, oral selective estrogen receptor (ER) degrader acting as a pure ER antagonist that can penetrate the brain barrier. EMBER-3 is the first prospective, randomized, phase 3 trial to report on the safety and efficacy of an oral selective ER degrader (imlunestrant) with or without abemaciclib in patients who experienced recurrent or progressing breast cancer on prior cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors.
This open-label, multicenter, multinational study compared PFS in 874 adults with ER+, human epidermal growth factor 2 (HER2)–negative advanced breast cancer. All patients had disease recurrence or progression during or after treatment with an aromatase inhibitor administered with or without a CDK4/6 inhibitor. Patients were randomized to three treatment groups: imlunestrant (n = 331; 138 had the ESR1 mutation), standard endocrine therapy by physician choice (n = 330; 118 had the ESR1 mutation), and imlunestrant plus oral abemaciclib (n = 213). The primary outcomes were PFS with imlunestrant versus standard therapy among patients with ESR1 mutations and among all patients and PFS with imlunestrant plus abemaciclib versus imlunestrant alone among all patients who had undergone concurrent randomization.
The study found that patients with an ESR1 mutation status had significantly longer PFS if they were treated with imlunestrant rather than standard therapy (5.5 vs. 3.8 months). At 19.4 months, patients treated with imlunestrant had a longer estimated mean survival time than those treated with standard therapy (7.9 vs. 5.4 months), and this was statistically significant (p < .001).
When imlunestrant plus abemaciclib was compared to imlunestrant alone, PFS was significantly improved in patients treated with imlunestrant plus abemaciclib (median, 9.4 vs. 5.5 months); this represented a 43% reduction in disease progression or death (hazard ratio, 0.57; 95% CI, 0.44–0.73; p < .001). Sixty-five percent of patients on the combination regimen had received prior CDK4/6 treatment with a PFS of 9.1 months.
“The consistency of these results across clinically relevant subgroups is reassuring given most patients eligible for second-line therapy have received a CDK4/6 inhibitor previously, and many currently available second-line therapies require biomarker selection,” says the lead author of the study, Komal Jhaveri, MD, a breast medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York.
Safety data showed imlunestrant to be well tolerated, with fatigue, diarrhea, and nausea as the most common adverse events. Patients experienced fewer grade 3 or higher adverse events with imlunestrant versus standard therapy (17.1% vs. 20.7%) and very low dose reduction and discontinuation rates. No concerning signals of bradycardia or ocular toxicities were present, and dyslipidemia rates were similar with imlunestrant monotherapy and standard therapy (7.3% vs. 8.2%), says Dr Jhaveri.
“Imlunestrant is potentially another monotherapy option for patients whose tumors harbor ESR1 mutations,” says Dr Jhaveri. “Both monotherapy and combination therapy were very well tolerated with very low discontinuation rates of 4% and 6%, respectively.”
Cancer , résumé, 2025