Elacestrant — Drug Monograph

Brand names: Orserdu

Drug class: Other

Mechanism of Action

Oral selective estrogen receptor degrader (SERD) that competitively binds estrogen receptor alpha (ERα) and promotes its proteasomal degradation, reducing total ERα protein levels. Unlike fulvestrant (injectable), elacestrant achieves oral bioavailability. Retains activity against ESR1-mutated ER, which confers resistance to aromatase inhibitors and CDK4/6 inhibitors.

FDA Indications

• ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer in postmenopausal women or adult men after ≥1 prior line of endocrine therapy including a CDK4/6 inhibitor (FDA approved January 2023; EMERALD trial: PFS HR 0.55 in ESR1-mutated population; 3.8 months PFS benefit; ESR1 ctDNA testing by Guardant360 CDx required)

Common Side Effects

• Nausea (35%)
• Musculoskeletal pain (29%)
• Vomiting (18%)
• Fatigue (18%)
• Hot flashes (17%)
• Constipation (15%)
• Elevated cholesterol/triglycerides
• Decreased appetite
• Dyspepsia

Clinical Pearl

Elacestrant is the first oral SERD approved, overcoming the injection burden of fulvestrant. The EMERALD trial showed clear benefit specifically in the ESR1-mutated subgroup (PFS HR 0.55) vs minimal benefit in ESR1 wild-type, making ESR1 ctDNA testing mandatory. Take with food to reduce nausea — the most common side effect.

Related Therapies & Mechanisms

• Capivasertib (Truqap) — Other · Breast
• Eribulin (Halaven) — Other · Breast
• Everolimus (Afinitor) — Other · Breast
• Adagrasib (Krazati) — Other