Dose Adjustment of Elacestrant

Elacestrant is the world’s first approved oral selective estrogen receptor degrader (SERD), indicated for the treatment of adult patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer harboring ESR1 gene mutations, particularly those with resistance to prior endocrine therapy.

Dose Adjustment of Elacestrant

Dose adjustments for oral elacestrant (once daily) are rarely required. Dosage modifications may be made in accordance with the guidelines below based on the severity of adverse reactions (ARs):

Mild to Moderate Reactions (Grade 1-2)

For Grade 1 adverse reactions, continue treatment at the current dose. In the event of Grade 2 adverse reactions, temporary treatment interruption is recommended until symptoms resolve to ≤ Grade 1 or baseline levels, after which treatment may be resumed at the original dose.

Severe Reactions (Grade 3)

If Grade 3 adverse reactions occur, discontinue treatment until symptoms resolve to ≤ Grade 1 or baseline levels, then resume treatment at a one dose level reduction. If Grade 3 toxicities recur, interrupt treatment again until recovery and resume at a further one dose level reduction.

Life-Threatening or Intolerable Reactions (Grade 4)

In the case of Grade 4 adverse reactions, discontinue treatment until symptoms resolve to ≤ Grade 1 or baseline levels, then resume treatment at a one dose level reduction. If Grade 4 or intolerable adverse reactions recur, permanent discontinuation of elacestrant is required.

Adverse Reactions of Elacestrant

Severe adverse reactions occurred in 12% of patients receiving elacestrant. Severe adverse reactions with an incidence of >1% included musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients treated with elacestrant, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one case each).

The most common adverse reactions (including laboratory abnormalities) with an incidence of ≥10% were: musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased aspartate aminotransferase (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased alanine aminotransferase (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite (15%), diarrhea (13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).

Use in Specific Populations

Lactation

Lactating women are advised to discontinue breastfeeding during elacestrant treatment and for 1 week after the last dose.

Hepatic Impairment

Elacestrant is not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). A dose reduction is required for patients with moderate hepatic impairment (Child-Pugh Class B).

The safety and efficacy of elacestrant in pediatric patients have not been established.