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Orserdu FDA Approved for ER-Positive, Advanced or Metastatic Breast Cancer with ESR1 Mutation

March 2023, Vol 13, No 3

On January 27, 2023, the FDA approved elacestrant (Orserdu; Stemline Therapeutics), an estrogen receptor (ER) antagonist, for the treatment of postmenopausal women or adult men with ER-positive, HER2-negative advanced or metastatic breast cancer and an ESR1 mutation whose disease progressed after ≥1 line of endocrine therapy.

At the same time, the FDA also approved the Guardant360 CDx assay, a companion diagnostic test, for identifying candidates for elacestrant therapy.

The FDA approval was based on results from the randomized, open-label, active-controlled, multicenter EMERALD clinical trial of women and men with ER-positive, HER2-negative advanced or metastatic breast cancer. All patients had disease progression after 1 or 2 lines of endocrine therapy, including 1 line containing a CDK4/6 inhibitor.

Of the 478 patients in the study, 228 (48%) patients had an ESR1 mutation. The patients were randomized (1:1) to elacestrant 345 mg orally once daily or to the investigator’s choice of endocrine therapy (ie, fulvestrant [Faslodex] or an aromatase inhibitor). Randomization was based on ESR1 mutation status using the Guardant360 CDx assay, previous treatment with fulvestrant, and visceral metastasis.

The progression-free survival (PFS) was significantly different between the patients with an ESR1 mutation and the intention-to-treat (ITT) population. Among the 228 patients with ESR1 mutations, the median PFS was 3.8 months (95% confidence interval [CI], 2.2-7.3) in the elacestrant arm versus 1.9 months (95% CI, 1.9-2.1) in the fulvestrant or aromatase inhibitor arm (hazard ratio, 0.55; 95% CI, 0.39-0.77; 2-sided P = .005).

In an exploratory analysis of PFS in the 250 (52%) patients without ESR1 mutations, the hazard ratio was 0.86 (95% CI, 0.63-1.19), indicating that the improvement in the ITT population was primarily based on the ESR1-positive status.

The most common (≥10%) adverse events were musculoskeletal pain, nausea, increased cholesterol, increased aspartate aminotransferase, increased triglycerides, fatigue, decreased hemoglobin, vomiting, increased alanine aminotransferase, decreased sodium level, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia.

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