FDA Approval Sought for Elacestrant in ER+/HER2- Advanced or Metastatic Breast Cancer

Developers of elacestrant are seeking FDA approval of the agent for the treatment of patients with ER-positive/HER2-negative advanced or metastatic breast cancer.

A new drug application (NDA) has been submitted to the FDA seeking approval of elacestrant for the treatment of patients with ER-positive/HER2-negative advanced or metastatic breast cancer, according to a joint announcement by the Menarini Group and Radius Health, Inc. The companies are requesting a priority review of the NDA.1

Data from the phase 3 EMERALD study support the NDA for elacestrant in patients with ER-positive/HER2-negative advanced or metastatic breast cancer. Recently, in the study, elacestrant demonstrated improvements in progression-free survival (PFS) and overall survival (OS) vs standard of care (SOC) endocrine therapy, meeting its coprimary end points. Elacestrant also showed better survival outcomes in the ESR1 mutation-positive subgroup compared with SOC.

“We enrolled and completed the EMERALD trial in a high-quality manner, delivered positive topline results, and prepared the submission of the NDA to the FDA. The submission is a significant milestone for both companies,” said Chhaya Shah, senior vice president of clinical and regulatory at Radius, in a press release.

The EMERALD study (NCT03778931) is a randomized, open-label, phase 3 trial in which 477 patients were randomized 1:1 to receive either elacestrant 400 mg or SOC endocrine therapy. The study population was made up of patients who had 1 to 2 prior lines of endocrine therapy, a CDK4/6 inhibitor, and 1 or more type of chemotherapy. The median age of the patient cohort was 64 years.

Primary results from the EMERALD study were presented in 2021 at the San Antonio Breast Cancer Symposium. The median PFS by independent review was 2.79 months with elacestrant vs 1.91 months with SOC (HR, 0.697; 95% CI, 0.552-0.880; = .0018). In a subgroup of patients with ESR1 mutations, elacestrant achieved a median PFS of 3.78 months vs 1.87 months with SOC, demonstrating a 45% reduction in the risk of disease progression or death in this subgroup (HR, 0.546; 95% CI, 0.387-0.768; P = .0005).2

Results presented during the 2022 American Society of Clinical Oncology Annual Meeting showed that in patients with no prior chemotherapy, PFS was improved with elacestrant vs SOC. The median PFS observed with elacestrant was 3.7 months vs 2.0 with SOC (HR, 0.68; 95% CI, 0.52-0.89; P = .004). The 6-month PFS rate was 38% with elacestrant vs 23% with SOC, and the 12-month PFS rates were 7% vs 12%, respectively.3

In the ESR1-positive subgroup, the median PFS observed in the elacestrant arm was 5.3 months vs 1.9 months with SOC (HR, 0.54; 95% CI, 0.36-0.80; P = .002). At 6 months, the PFS rate among patients treated with elacestrant was 44% compared with 24% in the SOC arm. The 12-month PFS rate was 31% with elacestrant vs 12% with SOC.

Treatment in the study appeared favorable with no treatment-related deaths in either group. In the elacestrant arm, the most common treatment-related adverse events were nausea (25.9%), fatigue (12.7%), and hot flush (11.1%).

"We are excited about the potential for elacestrant to be approved for treatment of patients with advanced or metastatic ER+/HER2- breast cancer, which constitutes about 70% of breast cancer and remains an area of significant unmet medical need." Barker Ergun, chief executive officer of Menarini, said, in the press release. "Elacestrant has shown statistically significant efficacy over current standard of care medications both for overall population and in patients whose tumors harbor an ESR1 mutation, one of the most difficult to treat mechanisms of acquired resistance that develops in the later stages of metastatic/advanced breast cancer.1


1. Menarini Group and Radius Health submit new drug application to the U.S. FDA for elacestrant. News release. Menarini Group and Radius Health. June 22, 2022. Accessed June 24, 2022. https://bit.ly/3bfbVZ2

2. Bardia A. Elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2-advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: Results of EMERALD phase 3 trial. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract GS2-02.

3. Kaklamani VG, Bardia A, Aftimoc PG, et al. Subgroup analysis of patients with no prior chemotherapy in EMERALD: A phase 3 trial evaluating elacestrant, an oral selective estrogen receptor degrader (SERD), versus investigator’s choice of endocrine monotherapy for ER+/HER2-advanced/metastatic breast cancer (mBC). J Clin Oncol. 2022; 40; 16:100-1100. doi: 10.1200/JCO.2022.40.16_suppl.1100