Elacestrant

• Class: Selective Estrogen Receptor Degrader (SERD)
• Mechanism of Action:
  
  Elacestrant binds to the estrogen receptor (ER) with high affinity, causing ER degradation and inhibiting estrogen signaling in ER-positive breast cancer cells. This leads to reduced tumor growth, especially in cases resistant to other endocrine therapies.

Indications

• Treatment of ER-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women and men, particularly after progression on prior endocrine therapy including aromatase inhibitors and CDK4/6 inhibitors.
• Approved for patients with ESR1 mutations, which often confer resistance to aromatase inhibitors.

Dosage

• Standard dose: 400 mg orally once daily with or without food.
• Dose modifications may be needed for adverse effects.

Pharmacokinetics

• Absorption: Oral, peak plasma concentration ~3–5 hours.
• Metabolism: Primarily via CYP3A4.
• Half-life: ~30 hours.
• Elimination: Mainly fecal.

Key Toxicities and Monitoring

• Common adverse effects:
  • Fatigue
  • Nausea
  • Musculoskeletal pain
  • Hot flashes
• Serious:
  • QT interval prolongation — monitor ECG and electrolytes especially in patients with risk factors.
• Monitoring:
  • ECG at baseline and periodically during therapy.
  • Liver function tests as clinically indicated.

Drug Interactions

• Substrate of CYP3A4 — avoid strong CYP3A4 inhibitors or inducers or adjust dose accordingly.
• Avoid concomitant use with other QT-prolonging drugs if possible.