Elacestrant (Orserdu) is the first oral selective estrogen receptor degrader (SERD). It was approved by the FDA in 2023 for the treatment of advanced or metastatic breast cancer that is estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and harbors ESR1 mutations. As an innovative endocrine therapy, its clinical application requires the establishment of a full-process monitoring system, ranging from genetic testing to long-term adverse reaction management.
What are the Precautions for Taking Elacestrant (Orserdu)?
Genetic Testing Verification
Before initiating treatment, the presence of missense mutations in the ligand-binding domain (codons 310-547) of ESR1 in plasma samples must be confirmed using an FDA-approved detection method (e.g., Guardant360 CDx).
If the test result is negative, the suitability of the treatment plan needs to be re-evaluated.
Dose Adjustment in Special Populations
Patients with Hepatic Impairment: For moderate hepatic impairment (Child-Pugh Class B), the dose should be adjusted to 258 mg once daily. The drug is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).
Standard Dosage
The recommended dose is 345 mg taken once daily with food. The tablets must be swallowed whole and should not be chewed, crushed, or split.
The medication should be taken at a fixed time each day. Taking it with food can significantly reduce the incidence of nausea and vomiting.
Dose Adjustment
First dose adjustment: If grade ≥3 adverse reactions occur, reduce the dose to 258 mg once daily (3 tablets of 86 mg each).
Second dose adjustment: If tolerance remains poor, further reduce the dose to 172 mg once daily (2 tablets of 86 mg each).
Criteria for permanent discontinuation: Further dose reduction is required, or grade 4 adverse reactions occur.
Drug Interactions
Contraindication with CYP3A4 Inhibitors: Concomitant use with strong or moderate CYP3A4 inhibitors (e.g., itraconazole, fluconazole) should be avoided, as this can lead to a significant increase in elacestrant plasma concentrations.
Restriction on CYP3A4 Inducers: Concomitant use with strong or moderate CYP3A4 inducers (e.g., rifampicin, efavirenz) is prohibited, as this may reduce drug exposure by 86%.
Reproductive Risk Management
Women of Childbearing Age: Effective contraceptive measures must be used during treatment and for 1 week after the last dose.
Male Patients: Male patients with partners of childbearing age must use contraceptive measures during treatment and for 1 week after discontinuing the drug.
Medication Monitoring for Elacestrant (Orserdu)
Lipid Metabolism Monitoring
Lipid levels should be monitored regularly before and during treatment. Clinical data show that the incidence of hypercholesterolemia is 30%, and the incidence of hypertriglyceridemia is 27%.
Dynamic Assessment of Liver Function
Aspartate transaminase (AST) (elevated in 29% of patients) and alanine transaminase (ALT) (elevated in 17% of patients) should be monitored. Corresponding dose adjustments should be made based on CTCAE (Common Terminology Criteria for Adverse Events) grading.
Hematological Parameter Tracking
Focus on monitoring hemoglobin levels (decreased in 26% of patients) and serum sodium levels (decreased in 16% of patients).
Cardiovascular Function Assessment
Although studies have shown a low risk of QTc interval prolongation at therapeutic doses, regular assessments at baseline and during treatment are still recommended.
