Orserdu Approved for ER+, HER2-, ESR1-Mutated Advanced or Metastatic Breast Cancer

In patients whose tumors had ESR1 mutations, elacestrant reduced the risk of progression or death by 45%.

The Food and Drug Administration (FDA) has approved Orserdu (elacestrant) for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive (+), human epidermal growth factor receptor 2 (HER2)-negative (-), ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy.

Elacestrant is an estrogen receptor antagonist that binds to estrogen receptor-alpha and inhibits 17β-estradiol mediated cell proliferation. The approval was based on data from the randomized, open-label, active-controlled, multicenter phase 3 EMERALD study (ClinicalTrials.gov Identifier: NCT03778931), which included 478 postmenopausal women and men with ER+, HER2- advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy; 228 patients had ESR1 mutations.

Patients were randomly assigned 1:1 to receive either elacestrant 345mg orally once daily (n=239), or investigator’s choice of endocrine therapy (n=239) which included fulvestrant (n=166) or an aromatase inhibitor (n=73; anastrozole, letrozole, or exemestane). The primary endpoint was progression free survival (PFS).

Among the 228 patients with ESR1 mutations, the median PFS was 3.8 months (95% CI, 2.2-7.3) in the elacestrant arm and 1.9 months (95% CI, 1.9-2.1) in the fulvestrant or aromatase inhibitor arm (hazard ratio [HR], 0.55 [95% CI, 0.39-0.77]; 2-sided P =.0005).

In an exploratory analysis of PFS in patients without ESR1 mutations (n=250), elacestrant was found to reduce the risk of progression or death by 14% (HR, 0.86 [95% CI, 0.63-1.19), indicating that improvement was attributed to results seen in the population with ESR1 mutations.

ESR1 mutations are a known driver of resistance to standard endocrine therapy, and so far, have been difficult to treat,” said Dr Aditya Bardia, MD, MPH, Director of Breast Cancer Research at Mass General Cancer Center, Associate Professor at the Medicine Department at Harvard Medical School, and Principal Investigator for the EMERALD trial. “The approval of elacestrant is welcomed as it offers a novel option for patients with ER+, HER2- metastatic breast cancer.”

The most common adverse reactions reported with elacestrant were musculoskeletal pain, nausea, increased cholesterol, increased AST/ALT, increased triglycerides, fatigue, decreased hemoglobin, vomiting, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia.

Orserdu is supplied as 86mg and 345mg tablets. Patients should be selected for treatment based on the presence of ESR1 mutations in a plasma specimen. The FDA has approved the Guardant360® CDx liquid biopsy test as a companion diagnostic for Orserdu.


  1. Stemline Therapeutics, a subsidiary of Menarini Group, receives US FDA approval for Orserdu (elacestrant) as the first and only treatment specifically indicated for patients with ESR1 mutations in ER+, HER2- advanced or metastatic breast cancer. News release. Stemline Therapeutics. January 27, 2023. Accessed January 30, 2023. https://www.businesswire.com/news/home/20230130005180/en/Stemline-Therapeutics-a-Subsidiary-of-Menarini-Group-Receives-U.S.-FDA-Approval-for-ORSERDU%E2%84%A2-elacestrant-as-the-First-and-Only-Treatment-Specifically-Indicated-for-Patients-with-ESR1-Mutations-in-ER-HER2–Advanced-or-Metastatic-Breast-Cancer.
  2. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. News release. US Food and Drug Administration. January 27, 2023. Accessed January 30, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-elacestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast-cancer.
  3. Guardant Health receives FDA approval for Guardant360® CDx as companion diagnostic for Menarini Group’s Orserdu™ for treatment of patients with ESR1 mutations in ER+, HER2- advanced or metastatic breast cancer. News release. Guardant Health, Inc. Accessed January 30, 2023. https://www.businesswire.com/news/home/20230126005956/en/Guardant-Health-receives-FDA-approval-for-Guardant360%C2%AE-CDx-as-companion-diagnostic-for-Menarini-Group%E2%80%99s-ORSERDU%E2%84%A2-for-treatment-of-patients-with-ESR1-mutations-in-ER-HER2–advanced-or-metastatic-breast-cancer.
  4. Orserdu. Package insert. Stemline Therapeutics; 2022. Accessed January 30, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217639s000lbl.pdf.