The Menarini Group (“Menarini”) and Radius Health, Inc. (“Radius”) (NASDAQ: RDUS) (collectively, the “Companies”) today announced that data from the pivotal phase 3 EMERALD clinical trial (NCT03778931) evaluating elacestrant as monotherapy vs. standard of care (SOC; fulvestrant or an aromatase inhibitor, AI) for the treatment of ER+/HER2- advanced or metastatic breast cancer were published in the Journal of Clinical Oncology.1 Elacestrant is the first oral selective estrogen receptor degrader (SERD) demonstrating a significant improvement in PFS vs. SOC with manageable safety in a phase 3 trial for patients with ER-positive/HER2-negative advanced breast cancer.
Dr. Aditya Bardia, breast medical oncologist and director of Breast Cancer Research at Mass General Cancer Center, Harvard Medical School, and principal investigator of the EMERALD clinical trial, commented, “There is an urgent unmet need for oral SERDs that are safe and effective against ER-positive metastatic breast cancer after progression on earlier lines of therapy, including CDK4/6 inhibitors. EMERALD is the first study to demonstrate a significant improvement in clinical outcomes with elacestrant, an oral SERD monotherapy, versus standard of care in a randomized, global phase III study for patients with ER-positive/HER2-negative advanced breast cancer. Further research is needed to develop combination therapies as well as evaluate novel endocrine therapies for patients with early breast cancer.”
As reported in the Journal of Clinical Oncology:
Patients had disease progression during or within 1 month following 1 or 2 lines of endocrine therapy and a cyclin-dependent kinase (CDK) 4/6 inhibitor. Patients could also have received 1 line of chemotherapy.
- 43% received 2 prior endocrine therapies for advanced breast cancer
- 22% received chemotherapy for advanced breast cancer
- 48% had detectable ESR1 mutation
Patients were randomized 1:1 to elacestrant (400 mg orally daily) or SOC choice of fulvestrant or AI; the protocol recommended that patients previously treated with fulvestrant receive AI and patients previously treated with AI receive fulvestrant.
Among the 477 patients enrolled in the trial, 239 received elacestrant.
Of the 165 patients who received fulvestrant all were pretreated with AI during the treatment for metastatic disease except n=6 who received fulvestrant. Of the 73 who received AI all were pretreated with fulvestrant except n=4.
Primary endpoints were PFS by blinded independent central review (IRC) in all patients and patients with detectable ESR1 mutations.
Elacestrant significantly reduced the risk of disease progression or death by 30% in all patients and by 45% in patients with an ESR1 mutation.
- PFS was prolonged in all patients (HR=0.70; 95% CI, 0.55–0.88; P=0.0018)
- PFS was prolonged in patients with ESR1 mutation (HR=0.55; 95% CI, 0.39–0.77; P=0.0005)
PFS rate at 12 months with elacestrant was 22.3% vs. 9.4% with SOC in the overall population, and 26.8% vs. 8.2% in the ESR1 mutation population
The most common treatment-emergent adverse events (AEs) in patients receiving elacestrant were mild or moderate gastrointestinal events.
Nausea was the most common AE.
- Any severity: 35% of patients receiving elacestrant and 16% fulvestrant, 25% receiving AI
- Severe (grade 3 or 4): 2.5% of patients receiving elacestrant and 0.9% receiving SOC
Treatment-related grade 3/4 AEs occurred in 7.2% of patients receiving elacestrant and 3.1% receiving SOC. Treatment was discontinued due to a treatment-related AEs in 3.4% receiving elacestrant and 0.9% receiving SOC.
A subgroup analysis of patients with no prior chemotherapy in EMERALD will be presented at ASCO 2022 (Abstract: 1100)
Menarini plans to pursue combination studies and study the potential of elacestrant to be effective in addressing the highest unmet needs for ER+/HER2-patients.