Elacestrant, sold under the brand name Orserdu, is an anticancer medication which is used in the treatment of breast cancer.
Elacestrant is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
It is specifically an antagonist of the estrogen receptor alpha (ERα).
Effective for ERS1 mutations.
Elacestrant is also a selective estrogen receptor degrader (SERD), in that it induces degradation of the ERα.
It causes degradation of the ER, thus inhibiting ER, mediated growth.
It is taken by mouth.
Bioavailability about 10%.
Protein binding about 99%.
Metabolism-Liver (major: CYP3A4, minor: CYP2A6, CYP2C9)
Elimination half-life 30–50 hours
Excretion-Feces (82%), urine (7.5%).
Can cross the blood brain barrier.
It is an antiestrogen, or an antagonist of the estrogen receptors, the biological targets of endogenous estrogens such as estradiol.
The most common side effects of elacestrant include musculoskeletal pain, nausea, increased cholesterol, elevated liver enzymes, increased triglycerides, fatigue, decreased hemoglobin, vomiting, increased ALT, increased AST, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flashes, and upset stomach.
Efficacy was evaluated in EMERALD , a randomized, open-label, active-controlled, multicenter trial that enrolled 478 postmenopausal women and men with ER-positive, HER2-negative advanced or metastatic breast cancer of which 228 participants had ESR1 mutations.
Participants were required to have disease progression on one or two prior lines of endocrine therapy, including one line containing a CDK4/6 inhibitor.
Eligible participants could have received up to one prior line of chemotherapy in the advanced or metastatic setting.
Participants were randomized (1:1) to receive elacestrant 345 mg orally once daily (n=239) or investigator’s choice of endocrine therapy (n=239), which included fulvestrant (n=166) or an aromatase inhibitor (n=73).
It is a nonsteroidal combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD).
Elacestrant has dose-dependent, tissue-selective estrogenic and antiestrogenic activities, with biphasic weak partial agonist activity at the ER at low doses and antagonist activity at higher doses.
It shows agonistic activity on bone and antagonistic activity on breast and uterine tissues.
Unlike the SERD fulvestrant, elacestrant is able to readily cross the blood-brain-barrier into the central nervous system, where it can target breast cancer metastases in the brain,
It is orally bioavailable and does not require intramuscular injection.
Side effects include ocular issues, decreasing heart rate, fatigue, and G.I. issues.