Elacestrant

Elacestrant is an anticancer (antineoplastic) medication used to treat adult men and postmenopausal women with advanced or metastatic breast cancer that has progressed after treatment with at least 1 line of endocrine treatment. It is a novel small molecule drug that was approved by the FDA in January 2023 to treat breast cancers that are estrogen receptor (ER) positive, human epidermal growth factor receptor-2 (HER2) negative, and have estrogen receptor 1 (ESR1) mutations, as confirmed by an FDA approved test.

Breast cancers are caused by gene mutations that cause uncontrolled growth of abnormal breast cells. Estrogen receptors are proteins on cell surfaces that stimulate cell growth and division in response to estrogen. Some types of breast cancers may result from excessive expression of a growth promoting protein HER2 in the cancer cells. Elacestrant is an estrogen receptor antagonist that prevents estrogen from stimulating cancer growth, but has no activity against HER2 protein, hence it is used for ER positive and HER2 negative breast cancers.

Elacestrant binds to estrogen receptor-alpha (ER-A), and induces degradation of ER-A, preventing its interaction with 17B estradiol, the predominant estrogen in women. This inhibits 17B estradiol-mediated growth and proliferation of cells and reduces tumor growth. Elacestrant has antitumor activity in ER positive HER2 negative breast cancers that have ESR1 mutations, and those that have developed resistance to an older estrogen receptor degrader drug fulvestrant, and cyclin-dependent kinase 4/6 (CDK4 and CDK6) inhibitor drugs.

Warnings

• Elacestrant can cause imbalance in blood fat (lipid) levels that may lead to dyslipidemia, including high cholesterol and high triglyceride levels. Evaluate the patient’s lipid levels before prescribing elacestrant and periodically during use.
• Elacestrant can cause fetal harm if administered during pregnancy. Screen women for pregnancy before prescribing elacestrant. Apprise pregnant women and women who may get pregnant of the potential for fetal risk. Advise women of pregnancy potential and men with women partners of reproductive potential to use effective contraception for the recommended periods.
• Avoid concurrent administration with strong or moderate CYP3A4 inhibitor drugs, they may increase exposure to elacestrant and increase the severity of its adverse effects.
• Avoid concurrent administration with strong or moderate CYP3A4 inducer drugs, they may reduce the efficacy of elacestrant.

Side effects of elacestrant

Common side effects of elacestrant include:

• Musculoskeletal pain
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Indigestion
• Decreased appetite
• Increase in cholesterol
• Increase in triglycerides
• Increase in liver enzyme aspartate aminotransferase (AST)
• Increase in liver enzyme alanine aminotransferase (ALT)
• Increase in creatinine
• Decrease in hemoglobin
• Decrease in sodium
• Fatigue
• Headache
• Dizziness
• Insomnia
• Shortness of breath
• Hot flush
• Rash
• Oral inflammation
• Gastroesophageal reflux disease

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady
• Severe nervous system reaction
• Serious eye symptoms

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Dosages of elacestrant

Tablet

Adult:

• Indicated for men or postmenopausal women with estrogen receptor positive (ER positive), HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy
• 345 mg orally once daily with food until disease progression or unacceptable toxicity

Dosage Modifications

Dose reduction recommendations for adverse reactions

• First dose reduction: 258 mg once daily
• Second dose reduction: 172 mg once daily
• Permanently discontinue if dose reduction to less than 172 mg/day required

Modifications for adverse reactions

• Grade 1: Continue at current dose level
• Grade 2: Consider dose interruption until recovery to Grade 1 or below, or baseline, then resume at same dose
• Grade 3
• Interrupt dose until recovery to Grade 1 or below, or baseline, then resume at next lower dose
• If Grade 3 toxicity recurs, interrupt until recovery to Grade 1 or below, or baseline, then resume elacestrant reduced by another dose level
• Interrupt dose until recovery to Grade 1 or below, or baseline, then resume at next lower dose
• Permanently discontinue if Grade 4 or intolerable adverse reaction recurs
• Mild (Child-Pugh A): No dosage adjustment recommended
• Moderate (Child-Pugh B): Reduce dose to 258 mg once daily
• Severe (Child-Pugh C): Avoid use; not studied

Dosing Considerations

• Select patients for treatment based on presence of ESR1 mutation(s) in plasma specimen using an FDA-approved test
• Verify pregnancy status of females of reproductive potential before initiating
• Obtain baseline lipid profile before initiating

Pediatric:

• Safety and efficacy not established

Overdose

There is no information available on the effects of elacestrant overdose. Overdose is likely to increase the risk of severe adverse effects such as disturbance of blood fat levels (dyslipidemia) and gastrointestinal disorders. Elacestrant overdose may be treated with symptomatic and supportive care.

Drug interactions with elacestrant

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Elacestrant has no known severe interactions with other drugs.
• Elacestrant has serious interactions with at least 110 different drugs.
• Moderate interactions of elacestrant include:
• atorvastatin
• clonidine
• colchicine
• digoxin
• irinotecan
• methotrexate
• sirolimus
• tacrolimus
• tazemetostat
• temsirolimus
• topotecan
• ubrogepant

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

Pregnancy and breastfeeding

• There is no available data on the safety of elacestrant use in pregnant women. Based on its mechanism of action and animal reproductive studies, elacestrant can cause fetal harm if administered during pregnancy.
• Women of reproductive potential and men with women partners of reproductive potential must use effective contraception during treatment and for one week after the last dose.
• Elacestrant may impair fertility in both men and women of reproductive potential.
• There is no information on the presence of elacestrant in breastmilk, or its effects on milk production or the breastfed infant. Nursing mothers should avoid breastfeeding during treatment and for one week after the final dose, because of the potential for serious adverse reactions on the breastfed infant.

Additional information about elacestrant

• Take elacestrant exactly as instructed with food at approximately the same time every day. Swallow the tablet whole, do not chew, crush or split.
• Do not take an additional dose if you have missed a dose for more than 6 hours or vomit after taking the drug, but skip the dose and continue with the next scheduled dose.
• You will need regular checkups to monitor your blood fat levels. Follow up with your physician and do not miss your appointments.
• Store elacestrant safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.

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Summary

Elacestrant is an anticancer (antineoplastic) medication used to treat adult men and postmenopausal women with advanced or metastatic breast cancer that has progressed after treatment with at least 1 line of endocrine treatment. Common side effects of elacestrant include musculoskeletal pain, nausea, vomiting, diarrhea, constipation, abdominal pain, indigestion, decreased appetite, increase in cholesterol, increase in triglycerides, increase in liver enzyme aspartate aminotransferase (AST), increase in liver enzyme alanine aminotransferase (ALT), and others.