Elacestrant Full Dose Recommendation
The recommended full dose of elacestrant is 345 mg orally once daily, taken continuously until disease progression or unacceptable toxicity. 1
FDA-Approved Dosing Regimen
Elacestrant 345 mg orally once daily is the standard dose approved by the US Food and Drug Administration for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer who have progressed after at least one line of endocrine therapy. 1
Treatment should continue until unequivocal disease progression or development of unacceptable toxicity. 1
Patient Population for Elacestrant Use
Elacestrant is specifically indicated only for patients with documented ESR1 mutations (in the estrogen receptor 1 gene), as the benefit-risk assessment in patients without ESR1 mutations was not favorable for FDA approval. 1
The drug is approved for use after progression on at least one prior line of endocrine therapy, including patients previously treated with CDK4/6 inhibitors and/or fulvestrant. 2, 1
In the pivotal EMERALD trial, 52% of patients had received prior CDK4/6 inhibitors and 52% had received prior SERD therapy, demonstrating efficacy even in heavily pretreated populations. 2
Clinical Efficacy Supporting This Dose
The 345 mg once daily dose demonstrated statistically significant improvement in progression-free survival in ESR1-mutated patients (HR 0.55; 95% CI 0.39-0.77; P=0.0005) compared to standard endocrine therapy. 1
The objective response rate was 19.4% overall in phase I studies at the 400 mg dose (which was the recommended phase II dose before final formulation adjustment to 345 mg), with 33.3% response rate specifically in patients with ESR1 mutations. 2
Clinical benefit rate at 24 weeks was 56.5% in patients with ESR1 mutations. 2
Dosing Administration Details
Elacestrant should be taken orally once daily as a continuous regimen without scheduled breaks. 1
The phase I study established that 400 mg once daily had an acceptable safety profile with no dose-limiting toxicities, which informed the final approved dose of 345 mg. 2
The drug is available in tablet formulation for oral administration. 2
Common Adverse Events and Management
The most common adverse events at the recommended dose include nausea (33.3%), increased blood triglycerides (25.0%), and decreased blood phosphorus (25.0%). 2
Most adverse events are grade 1-2 in severity, with upper gastrointestinal symptoms being the predominant side effects. 3, 2
More patients receiving elacestrant experienced nausea, vomiting, and dyslipidemia compared to standard endocrine therapy. 1
Critical Pitfall to Avoid
Do not use elacestrant in patients without confirmed ESR1 mutations, as the FDA approval is restricted to ESR1-mutated disease only—the benefit-risk assessment was not favorable in ESR1 wild-type patients despite statistical significance in the overall intention-to-treat population. 1
ESR1 mutation testing via circulating tumor DNA or tissue biopsy must be performed before initiating elacestrant therapy. 1