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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Tuesday, January 31, 2023
On January 27, the U.S. Food and Drug Administration (FDA) approved elacestrant (Orserdu) for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy. The FDA also approved the Guardant360 CDx assay as a companion diagnostic to identify patients with breast cancer for treatment with elacestrant.
Efficacy was evaluated in the EMERALD trial (ClinicalTrials.gov identifier NCT03778931), a randomized, open-label, active-controlled, multicenter trial that enrolled 478 postmenopausal women and men with ER-positive, HER2-negative advanced or metastatic breast cancer; a total of 228 patients had ESR1 mutations. Patients were required to have disease progression on one or two prior lines of endocrine therapy, including one line containing a CDK4/6 inhibitor.
Patients were randomly assigned (1:1) to receive elacestrant at 345 mg 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). Randomization was stratified by ESR1 mutation status (detected vs. not detected), prior treatment with fulvestrant (yes vs. no), and visceral metastasis (yes vs. no).
In the 228 patients (48%) with ESR1 mutations, median progression-free survival was 3.8 months (95% confidence interval [CI] = 2.2–7.3 months) with elacestrant and 1.9 months (95% CI = 1.9–2.1 months) with fulvestrant or an aromatase inhibitor (hazard ratio = 0.55 [95% CI = 0.39–0.77], two-sided P = .0005). An exploratory analysis of progression-free survival in the 250 patients (52%) without ESR1 mutations showed a hazard ratio of 0.86 (95% CI = 0.63–1.19), indicating the improvement in the intention-to-treat population was primarily attributed to the results seen in the ESR1-mutated population.
The most common adverse events (≥ 10%), including laboratory abnormalities, were musculoskeletal pain, nausea, increased cholesterol, increased aspartate aminotransferase, increased triglycerides, fatigue, decreased hemoglobin, vomiting, increased alanine aminotransferase, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia.
The recommended dose of elacestrant is 345 mg taken orally with food once daily until disease progression or unacceptable toxicity.
For more information, see the prescribing information.
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