FDA Approves Elacestrant for ER+/HER2–, ESR1-Mutated Advanced or Metastatic Breast Cancer


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

This article originally appeared on Onclive.com.

The FDA has approved elacestrant (Orserdu) for the treatment of postmenopausal women or adult men with estrogen receptor–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy.1

The FDA also approved the Guardant360 Dx assay as a companion diagnostic device to identify patients who are eligible to receive elacestrant.

The recommended elacestrant dose is 345 mg taken orally with food once daily until disease progression or unacceptable toxicity.

The regulatory decision was based on data from the randomized, open-label, active-controlled, multicenter phase 3 EMERALD trial (NCT03778931), in which the oral selective estrogen degrader (SERD; n = 115) reduced the risk of disease progression or death by 45% compared with fulvestrant (Faslodex) or an aromatase inhibitor (n = 113) in this population.2 The median progression-free survival with elacestrant was 3.8 months (95% CI, 2.2-7.3) vs 1.9 months (95% CI, 1.9-2.1) with the control (HR, 0.55; 95% CI, 0.39-0.77; P = .0005).

EMERALD enrolled patients with ER-positive/HER2-negative breast cancer who had progressed on 1 to 2 lines of endocrine therapy, including 1 line that contained a CDK4/6 inhibitor. Patients were able to have received up to 1 previous line of chemotherapy in either the advanced or metastatic setting.

Enrolled patients were randomly assigned in a 1:1 fashion to receive 345 mg of oral elacestrant per day (n = 239) or investigator’s choice of endocrine therapy, which could have been fulvestrant (Faslodex; n = 166) or an aromatase inhibitor such as anastrozole, letrozole, or exemestane (n = 73). Patients received treatment until progressive disease or intolerable toxicity.

Moreover, patients were stratified based on ESR1 mutational status (yes vs no), previous fulvestrant exposure (yes vs no), and the presence of visceral metastases (yes vs no).

ESR1 status was determined by blood circulating tumor DNA (ctDNA) using the Guardant360 CDx assay and was limited to ESR1 missense mutations in the ligand binding domain.

PFS by blinded imaging review committee assessment served as the major efficacy outcome of the trial. Overall survival was an additional efficacy outcome.

An exploratory analysis of PFS for patients without ESR1 mutations (n = 250) showed a HR of 0.86 (95% CI, 0.63-1.19), which is indicative that the improvement observed in the intention-to-treat population was primary attributed to the data observed in the ESR1-mutated population.

Among the patients with ESR1 mutations, the median age was 63 years (range, 28-89) and all were female. Moreover, 72% of patients were White, 5.7% were were Asian, 3.5% Black, and 0.4% were other; this information was not known or reported in 18.4% of patients. Moreover, 57% of patients had an ECOG performance status of 0 at baseline and 43% had a status of 1. Most patients (71%) had visceral disease (71%).

Additionally, 62% of patients had received 1 line of endocrine therapy and 39% had received 2 lines in the advanced or metastatic setting. All had previous treatment with a CDK4/6 inhibitor, 24% had prior fulvestrant, and 25% had prior chemotherapy.

Regarding safety, the most common adverse effects observed in at least 10% of patients treated with elacestrant, including laboratory abnormalities, were musculoskeletal pain, nausea, increased cholesterol, increased aspartate aminotransferase, increased triglycerides, fatigue, decreased hemoglobin, vomiting, increased alanine transaminase, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia.


  1. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. News release. FDA. January 27, 2023. Accessed January 23, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/
  2. Elacestrant (Orserdu) prescribing information. Stemline Therapeutics, Inc. January 2023. Accessed January 27, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217639s000lbl.pdf
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