What is elacestrant?
Elacestrant is the first oral selective estrogen receptor degrader (SERD) supplied as 86 mg and 345 mg tablets. Elacestrant antagonizes the estrogen receptor (ER) and exhibits dose-dependent degradation of ER[alpha]. It also inhibits estradiol-dependent, ER-directed gene transcription and tumor growth.
What is this approved for?
Elacestrant is approved for postmenopausal women or adult men with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression on at least one prior line of endocrine therapy. The Guardant360 CDx assay was also FDA-approved as a companion diagnostic to identify patients with ESR1 mutation.
The approval of elacestrant was supported by results of the EMERALD trial, a Phase III, randomized, open-label trial assessing postmenopausal women or men with ER+, HER2-negative advanced or metastatic breast cancer. Participants (N=478) had disease progression on 1-2 prior lines of endocrine therapy, including one line with a CDK4/6 inhibitor (J Clin Oncol 2022; doi: 10.1200/JCO.22.00338). Notably, 48 percent of patients were ESR1 mutation-positive, and 24 percent had prior fulvestrant, an injectable SERD.
Progression-free survival (PFS) was significantly improved in the elacestrant group on blinded imaging review committee assessment in the intention-to-treat (ITT) population and ESR1-mutated patients. In the ESR1-mutated group, elacestrant reduced risk of disease progression or death by 45 percent compared to active control, with median PFS of 3.8 months versus 1.9 months (HR: 0.55; 95% CI: 0.39-0.77, p=0.0005). The improved PFS in the ITT population was primarily influenced by the ESR1-mutated patients, given the HR 0.86 (95% CI: 0.63-1.19) among the ESR-wild type group. Importantly, elacestrant exhibited antitumor activity in difficult-to-treat tumors, including those with ESR1 mutation, and history of resistance to CDK4/6 inhibitors and even fulvestrant.
How do you administer this drug?
Take one 345 mg tablet once daily at approximately the same time each day until disease progression or unacceptable toxicity. Do not crush or split tablets. No premedications are required.
What are the common side effects associated with elacestrant (> or =10%)?
* Musculoskeletal pain (41%, Grade 3-4=7%)
* Nausea (35%, Grade 3-4=2.5%), vomiting (19%), diarrhea (13%), constipation (12%), dyspepsia (10%), and abdominal pain (11%)
* Increased cholesterol (30%)
* Increased aspartate aminotransferase (29%) and alanine aminotransferase (17%)
* Increased triglycerides (27%)
* Fatigue (26%)
* Decreased hemoglobin (26%)
* Decreased appetite (15%)
* Decreased sodium (16%)
* Increased creatinine (16%)
* Headache (12%)
* Hot flush (11%)
What are the uncommon side effects associated with elacestrant (less than 10%)?
Rash, gastroesophageal reflux disease, stomatitis, dizziness, insomnia, cough, and dyspnea occurred in <10 percent of patients.
Are there any important drug interactions I should be aware of?
Elacestrant is a major substrate of CYP3A4, and a minor substrate of CYP2A6 and CYP2C9. Use with CYP3A4 inducers will decrease elacestrant concentration and effectiveness and should be avoided. Use with CYP3A4 inhibitors should be avoided as it can increase systemic exposure and thus increase the risk of side effects. No dose adjustments are recommended for CYP3A4 interactions. Elacestrant is also a P-gp and BCRP inhibitor. Use with P-gp or BCRP substrates can increase exposure to those agents and may require dose adjustment.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
There are no recommended dose adjustments for renal impairment. For patients with moderate impairment (Child-Pugh class B), reduce dose to 258 mg daily. Avoid use in patients with severe hepatic impairment (Child-Pugh class C).
What should my patients know about elacestrant?
Patients should be aware of the most common side effects of elacestrant, including musculoskeletal pain, nausea, and other gastrointestinal side effects. Administration with food reduces nausea and vomiting. There is also a warning for dyslipidemia, and embryo-fetal toxicity. Females of child-bearing potential and male patients with female partners of child-bearing potential should be educated on the use of effective contraception during treatment and for at least 1 week after the last dose. Patients should also avoid breastfeeding while taking elacestrant.
What else should I know about elacestrant?
Due to a warning for dyslipidemia, patients should be monitored with a lipid panel at baseline and periodically throughout treatment.
What useful links are available regarding elacestrant?
* Elacestrant Prescribing & FDA Approval: https://tinyurl.com/5n7ypyp7
* EMERALD Trial: J Clin Oncol 2022; doi: 10.1200/JCO.22.00338
* Elacestrant: First Approval: Drugs 2023; doi: 10.1007/s40265-023-01861-0
Any ongoing clinical trials related to elacestrant?
A trial is ongoing for use of elacestrant in CDK4/6 inhibitor-naive ER-positive/HER2-negative advanced or metastatic breast cancer. Elacestrant is also being studied in combination with abemaciclib; samuraciclib, an oral CDK7 inhibitor; and onapristone, a progesterone receptor antagonist. A new trial not yet recruiting plans to assess elacestrant with or without triptorelin in premenopausal women with early-stage ER-positive/HER2-negative breast cancer. Find more information about these trials at ClinicalTrials.gov.
CASSANDRA PERKEY, PHARMD, BCOP, is Regional Clinical Pharmacist at the American Oncology Network. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/Manager, Clinical Pharmacy Services at Washington University School of Medicine. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, is Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine. He serves as the Pharmacy Forum column physician advisor.