Elacestrant hydrochloride, an estrogen receptor antagonist, is an antineoplastic agent.1
Elacestrant is used for the treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor type 2 (HER2)-negative, estrogen receptor 1 ( ESR1 )-mutated advanced or metastatic breast cancer in postmenopausal women or adult men whose disease has progressed following ≥1 line of endocrine-based therapy.1 Select patients for elacestrant therapy based on the presence of ESR1 mutation(s) in plasma specimen using an FDA-approved test.1
The current indication for elacestrant is based principally on the results of a randomized, multicenter, open-label, active-controlled, Phase 3 trial (EMERALD).1, 2 The trial enrolled 478 postmenopausal women and men with ER-positive, HER2-negative advanced or metastatic breast cancer with disease progression on 1 or 2 prior lines of endocrine therapy, including 1 line containing a CDK 4/6 inhibitor.1 One chemotherapy regimen in the advanced or metastatic setting was also permitted.1 Patients in the study were randomized in a 1:1 ratio to receive elacestrant 345 mg orally once daily or investigator's choice of endocrine therapy, which included fulvestrant or an aromatase inhibitor (anastrozole, letrozole, or exemestane).1 Randomization was stratified by ESR1 mutation status, prior treatment with fulvestrant, and presence of visceral metastases.1, 2 Treatment was continued until disease progression or unacceptable toxicity occurred.1
Of the 478 patients enrolled in the EMERALD study, 228 patients had ESR1 mutations.1 Among these patients, the median age was 63 years, 100% were female, 72% were white, and the baseline Eastern Cooperative Oncology Group performance status was 0 and 1 in 57 and 43% of patients, respectively.1 Seventy-one percent of patients had visceral disease, and 62 or 39% of patents had received 1 line or 2 lines of endocrine therapy in the advanced/metastatic setting, respectively.1 All patients had received prior treatment with a CDK 4/6 inhibitor, 25% had received prior chemotherapy, and 24% were previously treated with fulvestrant.1
The median duration of follow-up in the EMERALD study was 15.1 months.2 The primary efficacy outcome was progression-free survival (PFS), assessed by a blinded imaging review committee; overall survival was a key secondary efficacy outcome.1, 2 In patients with ESR1 mutations, the median PFS was longer with elacestrant (3.8 months) than with endocrine therapy (1.9 months); PFS events occurred in 62 (54%) patients in the elacestrant group versus 78 (69%) patients in the endocrine therapy group.1, 2 In the ESR1 mutation cohort, overall survival events were not substantially different between groups, and occurred in 61 (53%) patients in the elacestrant group versus 60 (53%) patients in the endocrine therapy group.1
A clinical practice guideline update from the American Society of Clinical Oncology (ASCO) provides recommendations for testing and treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer.3
In patients with ER-positive, HER2-negative metastatic breast cancer, ASCO recommends routine testing for the emergence of ESR1 mutations at disease recurrence or progression on endocrine therapy (administered with or without a CDK4/6 inhibitor).3 Testing with an approved assay should be performed on blood or tissue obtained at the time of progression.3 The preferred testing method is blood-based circulating tumor (ctDNA).3
Patients with advanced breast cancer previously treated with endocrine therapy and a CDK4/6 inhibitor have several therapy options if they choose to continue endocrine-based treatment.3 For patients with ESR1 wild-type tumors who were previously treated with a CDK4/6 inhibitor, appropriate subsequent endocrine therapy options include monotherapy with fulvestrant, an aromatase inhibitor, or tamoxifen, or endocrine therapy in combination with targeted agents such as alpelisib (for those with phosphatidylinositol-3-kinase catalytic subunit α [ PIK3CA ]-mutated tumors) or everolimus.3 For patients with a detectable ESR1 mutation who were previously treated with a CDK4/6 inhibitor, treatment options include elacestrant, or other endocrine therapy either alone or in combination with targeted agents such as alpelisib (for those with PIK3CA -mutated tumors) or everolimus.3 ASCO states that elacestrant should not be used in combination with targeted agents, as efficacy and safety data on this approach are lacking.3
Administer orally once daily at approximately the same time each day.1
Administer elacestrant with food to reduce nausea and vomiting.1
Swallow tablets whole; do not chew, crush, or split prior to swallowing.1 Do not take any tablets that are broken, cracked, or look damaged.1
If a dose is missed for >6 hours or vomiting occurs, skip the dose and take the next dose on the following day at its regularly scheduled time.1
Store tablets at 20-25°C (excursions permitted between 15-30°C).1
Dosage of elacestrant hydrochloride is expressed in terms of elacestrant.1
For the treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1 -mutated advanced or metastatic breast cancer, the recommended dosage of elacestrant is 345 mg orally once daily with food.1 Continue treatment until disease progression or unacceptable toxicity occurs.1
Dosage Modification for Toxicity
If adverse reactions occur during elacestrant therapy, temporary interruption, dosage reduction, and/or permanent discontinuance of the drug may be necessary.1 If dosage modification is required, reduce the dosage of elacestrant as described below (see Table 1).1
Dosage Reduction Level | Recommended Dosage |
|---|---|
First dose reduction | 258 mg (three 86 mg tablets) orally once daily |
Second dose reductiona | 172 mg (two 86 mg tablets) orally once daily |
aPermanently discontinue elacestrant if further dose reduction below 172 mg is required.1
Recommended dosage modifications for adverse reactions based on severity are listed below (see Table 2).1
Severity | Recommendation |
|---|---|
Grade 1 | Continue at current dosage level. |
Grade 2 | Consider interruption until recovery to grade 1 or less or baseline, then resume at the same dosage level |
Grade 3 | Interrupt therapy until recovery to grade 1 or less or baseline, then resume at the next lower dosage level If grade 3 toxicity recurs, interrupt therapy until recovery to grade 1 or less or baseline, then resume therapy reduced by another dosage level |
Grade 4 | Interrupt therapy until recovery to grade 1 or less or baseline, then resume therapy reduced by 1 dosage level. If grade 4 or intolerable adverse reaction recurs, permanently discontinue elacestrant. |
No dosage adjustment is necessary in patients with mild hepatic impairment (Child-Pugh class A).1
Reduce elacestrant dosage to 258 mg once daily in patients with moderate hepatic impairment (Child-Pugh class B).1
Avoid use of elacestrant in patients with severe hepatic impairment (Child-Pugh class C).1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Hypercholesterolemia and hypertriglyceridemia have occurred in 30 and 27% of patients, respectively, in elacestrant clinical trials; grade 3 and 4 hypercholesterolemia and hypertriglyceridemia occurred in 0.9 and 2.2% of patients, respectively.1
Monitor lipid profile prior to starting elacestrant and periodically during treatment.1
Fetal/Neonatal Morbidity and Mortality
Elacestrant use during pregnancy can cause fetal harm based on findings from animal studies and the mechanism of action of the drug.1 Administration of elacestrant to pregnant rats during the period of organogenesis caused structural abnormalities and embryofetal death at maternal exposures below the recommended dose based on AUC.1
Verify pregnancy status in females of reproductive potential prior to initiating elacestrant.1 Apprise patients of the potential hazard to the fetus if elacestrant is used during pregnancy.1 Animal studies indicate that elacestrant may impair fertility in females and males of reproductive potential.1 Advise females of reproductive potential, and males with female partners of reproductive potential, to use effective contraception during treatment and for 1 week after the last dose of elacestrant.1
Elacestrant use during pregnancy can cause fetal harm based on findings in an animal study and the mechanism of action of the drug.1
Human data on elacestrant use during pregnancy are not available to determine the drug-associated risk.1 Administration of oral elacestrant to pregnant rats during the period of organogenesis resulted in structural abnormalities and embryofetal death at maternal exposures below the recommended dose based on AUC.1 Maternal toxicity (reduced weight gain, low food consumption, red vulvar discharge) was also observed in rats.1
Verify pregnancy status in females of reproductive potential prior to initiating elacestrant.1 Apprise patients of the potential hazard to the fetus if elacestrant is used during pregnancy.1
It is unknown whether elacestrant distributes into human milk, or affects milk production or the breast-fed infant.1
Because of the potential for serious adverse reactions in breast-fed infants, advise women to not breast-feed during treatment with elacestrant and for 1 week after the last dose.1
Females and Males of Reproductive Potential
Perform pregnancy testing in females of reproductive potential prior to initiating elacestrant.1
Animal studies indicate that elacestrant may impair fertility in females and males of reproductive potential.1
Advise females of reproductive potential, and males with female partners of reproductive potential, to use effective contraception during treatment with elacestrant and for 1 week after the last dose.1
Safety and efficacy of elacestrant in pediatric patients have not been established.1
In the EMERALD trial, 43 and 17% of patients were ≥65 and ≥75 years of age.1 There were no overall differences in the safety or efficacy of elacestrant between patients ≥65 years and younger adults.1 There was an insufficient number of patients ≥75 years of age to assess age-related differences in safety or efficacy.1
No clinically important differences in elacestrant pharmacokinetics were observed based on age (range 24-89 years).1
No clinically important differences in elacestrant peak plasma concentrations and AUC were observed in patients with mild hepatic impairment.1
The AUC of elacestrant increased by 83% in patients with moderate hepatic impairment.1
Avoid use of elacestrant in patients with severe hepatic impairment (Child-Pugh class C); the drug has not been studied in this population.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
Adverse effects (including laboratory abnormalities) reported in ≥10% of patients receiving elacestrant were musculoskeletal pain, nausea, vomiting, increased cholesterol, increased AST/ALT, increased triglycerides, fatigue, decreased hemoglobin, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia.1
Elacestrant is primarily metabolized by cytochrome P-450 (CYP) isoenzyme 3A4, and by isoenzymes 2C9 and 2A6 to a lesser extent.1
Elacestrant is a CYP3A4 substrate.1 Elacestrant is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A.1 Elacestrant is not an inducer of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, or CYP3A.1
Elacestrant is an inhibitor of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).1
Elacestrant is a substrate for organic anion transporting polypeptide (OATP) 2B1, but not P-gp.1
Elacestrant does not inhibit organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 2, OCT1, OATP1B1, OATP1B3, multidrug and toxin extrusion (MATE) 1, MATE2K, or OATP2B1.1
Drugs Affecting or Affected by Hepatic Microsomal Enzymes
Moderate and Strong CYP3A4 Inhibitors
Concomitant use of elacestrant with a moderate or strong CYP3A inhibitor may increase elacestrant exposure and consequently increase the risk for toxicity.1
When itraconazole (strong CYP3A inhibitor) was administered concomitantly with elacestrant (172 mg once daily), peak plasma concentrations and area under the concentration-time curve (AUC) of elacestrant increased 4.4 and 5.3 fold, respectively.1
When fluconazole (moderate CYP3A inhibitor) was administered concomitantly with elacestrant (345 mg single dose), peak plasma concentrations and AUC of elacestrant increased 1.6 and 2.3 fold, respectively.1
Avoid concomitant use of elacestrant with moderate or strong CYP3A inhibitors.1
Moderate and Strong CYP3A4 Inducers
Concomitant use of elacestrant with a moderate or strong CYP3A inducer may decrease elacestrant exposure and consequently reduce the efficacy of elacestrant.1
When rifampin (strong CYP3A inducer) was administered concomitantly with elacestrant (345 mg single dose), peak plasma concentrations and AUC of elacestrant were decreased by 73 and 86%, respectively.1
When efavirenz (moderate CYP3A inducer) is administered concomitantly with elacestrant (345 mg single dose), peak plasma concentrations and AUC of elacestrant are predicted to decrease by 44-63 and 55-73%, respectively.1
Avoid concomitant use of elacestrant with moderate or strong CYP3A inducers.1
Drugs Affecting or Affected by Transport Systems
P-gp or BCRP Substrates
Elacestrant may increase the plasma concentrations of a P-gp or BCRP substrate and consequently increase the risk for adverse reactions associated with the substrate.1
When digoxin (P-gp substrate) was administered concomitantly with elacestrant (345 mg single dose), peak plasma concentrations and AUC of digoxin increased 1.3 and 1.1 fold, respectively.1
When rosuvastatin (BCRP substrate) was administered concomitantly with elacestrant (345 mg single dose), peak plasma concentrations and AUC of rosuvastatin increased 1.5 and 1.2 fold, respectively.1
Reduce the dosage of P-gp or BCRP substrates as recommended in their prescribing information when minimal concentration changes may lead to serious or life-threatening adverse reactions.1
No clinically important differences in elacestrant pharmacokinetics were observed when elacestrant was used concomitantly with cimetidine (a weak CYP3A inhibitor).1
No clinically important differences in elacestrant pharmacokinetics were observed when elacestrant was used concomitantly with omeprazole (a gastric acid-reducing agent).1
No clinically important differences in elacestrant pharmacokinetics were observed when elacestrant was used concomitantly with warfarin (a highly protein-bound drug).1
Elacestrant is an estrogen receptor antagonist that binds to and degrades estrogen receptor-alpha (ERα).1 In estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer cells, elacestrant inhibits 17β-estradiol mediated cell proliferation at concentrations that result in ERα degradation.1 Elacestrant exhibits antitumor activity including in ER-positive, HER2-negative breast cancer models resistant to fulvestrant and cyclin-dependent kinase 4/6 inhibitors, as well as in those with estrogen receptor 1 ( ESR1 ) gene mutations.1
The exposure-response relationships of elacestrant and the time course of pharmacodynamics have not been fully characterized.1 Peak plasma concentrations and AUC of elacestrant increase more than proportionally across the dosage range of 43-862 mg once daily (0.125-2.5 times the approved recommended dosage).1 Steady state is reached by day 6.1 The time to achieve peak plasma concentration ranges from 1-4 hours.1 The oral bioavailability of elacestrant is approximately 10%.1 Administration of elacestrant 345 mg with a high-fat meal (800-1000 calories with 50% of calories from fat) increased the peak plasma concentration and AUC of elacestrant by 42 and 22%, respectively, compared to the fasted state.1 Plasma protein binding of elacestrant is >99% and is independent of drug concentration.1 Elacestrant is primarily metabolized by cytochrome P-450 (CYP) isoenzyme 3A4, and by CYP isoenzymes 2C9 and 2A6 to a lesser extent.1 Following a single radiolabeled oral dose of elacestrant 345 mg, 82% (34% unchanged) and 7.5% (<1% unchanged) was recovered in feces and urine, respectively.1 The elimination half-life of elacestrant is 30-50 hours.1 The pharmacokinetics of elacestrant do not appear to be affected by age (24-89 years), sex, or body weight (41-143 kg).1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Elacestrant is available through specialty pharmacies and specialty distributors.2 Clinicians may consult the Orserdu® manufacturer website ([Web]) for more information.2
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 86 mg (of elacestrant) | Orserdu® | Stemline Therapeutics |
345 mg (of elacestrant) | Orserdu® | Stemline Therapeutics |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions February 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Stemline Therapeutics, Inc. Orserdu® (elacestrant) ORAL prescribing information. 2023 Nov. [Web]
2. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol . 2022;40(28):3246-3256.
3. Burstein HJ, DeMichele A, Somerfield MR, Henry NL; Biomarker Testing and Endocrine and Targeted Therapy in Metastatic Breast Cancer Expert Panels. Testing for ESR1 mutations to guide therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: ASCO guideline rapid recommendation update. J Clin Oncol . 2023;41(18):3423-3425.
4. Stemline ARC®. Orserdu® Assistance and Ordering. Accessed 2023 Sep 27 Sep. From Orserdu® for US Healthcare Professionals website. http://stemlinearc.com/hcp/orserdu/financial-assistance-and-ordering-information/