After clinical trial outcomes demonstrated a statistically significant difference in progression-free survival in a subgroup of patients with estrogen receptor (ER)-positive, HER2-negative, ESR1-altered disease, the U.S. Food and Drug Administration granted elacestrant’s (Orserdu™) application priority review and fast-track designation, with regular approval in January 2023.
Mechanism of Action
Elacestrant binds to ER alpha, which disrupts downstream signaling and promotes ER turnover. Breast cancer patients that have an altered ESR1 gene and are ER+. HER2- that have become resistant to fulvestrant and CDK4/6 inhibitors have shown antitumor activity when using elacestrant.
Postmenopausal females or males with ER-positive, HER2-negative, ESR1-altered advanced or metastatic breast/chest cancer who have progressed after one line of endocrine therapy. Patients must have also completed an FDA-approved companion diagnostic test to identify an ESR1 alteration to be eligible for treatment with elacestrant.
Dosing and Administration
Take 345 mg orally with food at approximately the same time once each day. Do not crush, chew, or split any pills. If you miss a dose by more than six hours or vomit it, skip it and take your next dose the following day at its regularly scheduled time. Elacestrant is available in 345 mg and 86 mg tablets for various dose reductions.
The most common adverse reactions reported in more than 10% of patients during elacestrant’s clinical trials were abdominal pain, constipation, decreased appetite, diarrhea, dyspepsia, fatigue, headache, hot flush, musculoskeletal pain, nausea, and vomiting. Lab abnormalities included increased cholesterol, AST, ALT, triglycerides, and creatine and decreased hemoglobin and sodium.
Elacestrant is a CYP3A4 substrate. Using it in combination with strong or moderate CYP3A4 inducers increases its effect and the risk of adverse reactions. Conversely, strong or moderate CYP3A4 inhibitors will decrease its effect.
Verify pregnancy status in females of reproductive potential, and collect a lipid panel because of the risk for dyslipidemia. Incremental lipid tests may be needed throughout treatment. Review patients’ medical history for hepatic impairment. Review patients’ medication list for CYP3A4 inducers or inhibitors.
Patient and Caregiver Education
Because of the risk for fetal harm in patients of reproductive potential, patients should use effective contraception during treatment and at least one week after the last dose. Do not breastfeed while on elacestrant.
Educate patients on how to take elacestrant safely. Review their lab monitoring plan, possible adverse reactions, and when and how to report any symptoms.
Avoid using elacestrant in patients with severe hepatic impairment. For moderate hepatic impairment, reduce the dose to 258 mg once a day. Elacestrant’s trials did not identify any clinically significant differences in outcomes among older adults.
Elacestrant requires safe handling during administration and disposal because of its risk for fetal harm.
Stemline ARC Patient Advocates offers reimbursement assistance and other services. Call 833-478-3654 or visit stemlinearc.com.