On Jan. 27, 2023, elacestrant (Orserdu™, Stemline Therapeutics, Inc.) was approved for the treatment of postmenopausal women or adult men with ER-positive, HER2-negative advanced or metastatic breast cancer that has an ESR1 mutation and has progressed following at least 1 line of endocrine therapy. A companion diagnostic, the Guardant360 CDx assay, should be used to identify suitable patients.¹

Elacestrant is the first oral selective estrogen receptor degrader (SERD) to be approved. Fulvestrant, an intramuscular injectable, was the only SERD available prior to this. The ESR1 gene codes for the estrogen receptor, and mutations are drivers of resistance to endocrine therapies.² Thus, the approval of an oral drug that remains active in the presence of ESR1 mutations provides a novel therapeutic option for patients.

Elacestrant may cause hypercholesterolemia and hypertriglyceridemia, so lipid profiles should be monitored before and during treatment. Other possible adverse effects were generally mild and manageable³ and included gastrointestinal disturbances, decreased appetite, musculoskeletal pain, hot flushes, and fatigue. Increased aspartate aminotransferase and alanine aminotransferase and decreased sodium, creatinine, and hemoglobin were also noted in a clinical trial.¹

The recommended oral dosage is 345 mg taken with food once a day. Adverse reactions may necessitate dose interruption, reduction, or permanent discontinuation.

Avoid use during pregnancy or in patients who have severe hepatic impairment (Child-Pugh C). Patients with moderate hepatic impairment will need a reduced dose. The drug should not be given with strong or moderate CYP3A4 inducers or inhibitors.

The approval was based on results from the EMERALD trial of 478 patients with ER-positive, HER2-negative breast cancer who had disease progression on 1 or 2 prior lines of endocrine therapy; all patients had been treated with a CDK4/6 inhibitor. ESR1 mutations were detected in 228 patients. Participants were randomized to receive either oral elacestrant or standard of care (SOC) treatment with injectable fulvestrant, anastrozole, letrozole, or exemestane.³ Progression-free survival (PFS) was sigficantly better with elacestrant in both the overall cohort (30% relative reduction in progression or death) and in the ESR1-positive subgroup (45% relative reduction). This superior PFS with elacestrant was also found in a secondary analysis with the fulvestrant subgroup.

References

1. Orserdu (elacestrant). Prescribing information. Stemline Therapeutics, Inc; 2023. Accessed February 13, 2023. https://drive.google.com/file/d/1aE_1XYQqLKDZZZQIOMqU-a-VhQUGIT8w/view
2. Brett JO, Spring LM, Bardia A, Wander SA. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):85. doi:10.1186/s13058-021-01462-3
3. 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. doi:10.1200/jco.22.00338