EMA Accepts Marketing Authorization Application for Elacestrant in ER+/HER2- Advanced Breast Cancer


The European Medicines Agency has validated a marketing authorization application for elacestrant for estrogen receptor–positive, HER2-negative advanced or metastatic breast cancer.

Elcin Barker Ergun

Elcin Barker Ergun

The European Medicines Agency (EMA) has validated a marketing authorization application (MAA) for elacestrant, a selective estrogen receptor degrader (SERD), for patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer.1

The MAA is based on findings from the pivotal phase 3 EMERALD study (NCT03778931), which demonstrated a 30% reduction in the risk of disease progression following treatment with the SERD (n = 239) compared with standard of care (SOC; n = 238) per blinded independent central review (BICR; HR, 0.70; 95% CI, 0.55-0.88; P = .0018).2

The median progression-free survival (PFS) with elacestrant was 2.8 months vs 1.9 months with SOC. Additionally, the 12-month PFS rates were 22.3% (95% CI, 15.2%-29.4%) and 9.4% (95% CI, 4.0%-14.8%), respectively.

Among patients who harbored baseline ESR1 mutations (n = 228), elacestrant (n = 115) led to a 45% reduction in the risk of disease progression vs SOC (n = 113; HR, 0.55; 95% CI, 0.39-0.77; P = .0005). The median PFS in the elacestrant arm was 3.8 months vs 1.9 months in the SOC arm. The 12-month PFS rates were 26.8% (95% CI, 16.2%-37.4%) and 8.2% (95% CI, 1.3%-15.1%), respectively.

Elacestrant, if approved, would be the first oral SERD available for use in patients in need of second-line and third-line treatment for ER-positive, HER2-negative advanced or metastatic breast cancer in the European Union.

“There is a major unmet need in the treatment of advanced or metastatic ER-positive/HER2-negative breast cancer after resistance builds in the earlier lines of treatment,” Elcin Barker Ergun, chief executive officer of the Menarini Group, stated in a press release. “The acceptance of our application for review by the EMA represents a significant step for our company and we look forward to working with the agency to potentially bring elacestrant to patients suffering from second- and third-line ER-positive, HER2-negative advanced or metastatic breast cancer in Europe.”

On August 11, 2022, the FDA granted priority review to a new drug application seeking the approval of elacestrant in the same population based on findings from EMERALD.3

Eligible patients had to have progressed or relapsed on, or following, 1 or 2 lines of endocrine therapy for advanced disease, and 1 of these lines of treatment had to have been given in combination with a CDK4/6 inhibitor. Patients also needed to have received at least 1 line of chemotherapy for advanced disease, and an ECOG performance status of 0 or 1.

Patients were randomly assigned 1:1 to receive 400 mg of elacestrant daily or investigator’s choice of SOC treatment in the form of fulvestrant (Faslodex), anastrozole, letrozole, or exemestane.

The coprimary end points of the trial were the PFS in all patients and in those with ESR1-mutated tumors. Secondary end points included overall survival (OS) in both populations, PFS and OS in those without ESR1 mutations, investigator-assessed PFS, overall response rate, duration of response, clinical benefit rate, and safety.

At an interim analysis, the median OS was not calculated in either arm, but favored elacestrant in both the intention-to-treat (HR, 0.75; 95% CI, 0.54-1.04; P = .08) and ESR1-mutant (HR, 0.59; 95% CI, 0.36-0.96; P = .03) populations.

Regarding safety, elacestrant displayed a manageable toxicity profile consistent with what has been reported with other endocrine therapies.

Additional post-hoc analysis from the study will be presented at the 2022 ESMO Congress in September.


  1. Menarini Group’s Elacestrant Marketing Authorization Application Accepted for Review by the European Medicines Agency (EMA) for the Treatment of ER+/HER2- Advanced or Metastatic Breast Cancer. News release. Menarini. Published August 19, 2022. Accessed August 22, 2022. https://bit.ly/3dO9puc
  2. Bidard F-C, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. Published online May 18, 2022. doi:10.1200/JCO.22.00338
  3. Menarini Group’s elacestrant granted priority review by the US FDA for patients with ER+/HER2- advanced or metastatic breast cancer. News release. Menarini Industrie Farmaceutiche Riunite. August 11, 2022. Accessed August 22, 2022. https://prn.to/3bQQfD9
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