EMA accepts marketing authorization application for Elacestrant for the treatment of advanced ER+/HER2- breast cancer

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

The European Medicines Agency (EMA) has validated a Marketing Authorization Application (MA) for elacestrant, a Selective Estrogen Receptor Degrader (SERD), for breast cancer patients advanced or metastatic estrogen receptor (ER) positive, HER2 negative.1

The marketing authorization is based on the results of the pivotal phase 3 EMERALD study (NCT03778931), which demonstrated a 30% reduction in the risk of disease progression after treatment with SERD (n = 239) compared to standard treatment (SOC; n=238) by blinded independent central review (BICR; HR, 0.70; 95% CI, 0.55-0.88; P = 0.0018).2

The median progression-free survival (PFS) with elacestrant was 2.8 months versus 1.9 months with SOC. Additionally, the 12-month PFS rates were 22.3% (95% CI, 15.2% to 29.4%) and 9.4% (95% CI, 4.0% at 14 .8%), respectively.

Of the patients who housed the baseline CSR1 mutations (n=228), elacestrant (n=115) resulted in a 45% reduced 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 versus 1.9 months in the SOC arm. PFS rates at 12 months 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 requiring second- and third-line treatment for advanced or metastatic ER-positive, HER2-negative 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 the emergence of resistance in first lines of treatment,” said Elcin Barker Ergun, Chief Executive Officer of the Menarini group, in a press release. Release. “The acceptance of our application for review by the EMA represents an important milestone for our company and we look forward to working with the agency to potentially bring elacestrant to ER-positive, HER2 second and third line patients. -negative advanced or metastatic breast cancer in Europe.

On August 11, 2022, the FDA Granted Priority Review to New Drug Application Seeking Approval of Elacestrant in the same population based on EMERALD results.3

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

Patients were randomized 1:1 to receive elacestrant 400 mg daily or SOC treatment of investigator’s choice as fulvestrant (Faslodex), anastrozole, letrozole, or exemestane.

The co-primary endpoints of the trial were PFS in all patients and in those CSR1– mutated tumors. Secondary endpoints included overall survival (OS) in both populations, PFS and OS in those without CSR1 mutations, investigator-assessed PFS, overall response rate, duration of response, clinical benefit rate and safety.

In an interim analysis, median OS was not calculated in either arm, but favored elacestrant in both treatment intentions (HR, 0.75; 95% CI, 0.54-1, 04; P = .08) and CSR1-mutant (RR, 0.59; 95% CI, 0.36-0.96; P = 0.03) populations.

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

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


  1. The marketing authorization application for Elacestrant from the Menarini group has been accepted for review by the European Medicines Agency (EMA) for the treatment of advanced or metastatic ER+/HER2- breast cancer. Press release. Menarini. Published August 19, 2022. Accessed August 22, 2022. https://bit.ly/3dO9puc
  2. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (Selective Oral Estrogen Receptor Degrader) Versus Standard Hormone 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. The Menarini group’s elacestrant has been granted priority review by the US FDA for patients with advanced or metastatic ER+/HER2- breast cancer. Press release. Menarini Industrie Farmaceutiche Riunite. August 11, 2022. Accessed August 22, 2022. https://prn.to/3bQQfD9