For patients with locally advanced or metastatic estrogen receptor (ER)–positive, HER2-negative breast cancer, the frontline standard of care is endocrine therapy, often combined with a CDK4/6 inhibitor. However, disease progression leads to endocrine resistance, necessitating alternative treatments. The FDA's approval of elacestrant (Orserdu) in early 2023 provides a new oral therapy option for patients with ESR1 mutations, offering a significant improvement in progression-free survival (PFS) compared to traditional treatments like fulvestrant.
Elacestrant's approval was supported by the phase 3 EMERALD trial, which demonstrated significant PFS improvements in patients with ESR1 mutations. The trial involved 478 participants, with 228 having ESR1 mutations, showing a median PFS of 3.8 months for elacestrant versus 1.9 months for fulvestrant/aromatase inhibitor cohort.
Elacestrant is a nonsteroidal oral SERD that degrades the ER α in a dose-dependent manner, inhibiting estradiol-dependent ER-directed gene transcription and tumor growth. The recommended dose is one 345-mg tablet daily, with potential side effects including musculoskeletal pain, nausea, and increased cholesterol levels. Despite these, the side effects are generally manageable, with patients tolerating the agent well.
The shift to oral oncolytics like elacestrant represents a significant advancement in patient care, offering a less painful and more convenient treatment option compared to intramuscular injections of fulvestrant. This development not only improves the quality of life for patients but also opens the door for further research and integration of oral SERDs into clinical practice, with ongoing studies evaluating the efficacy of elacestrant paired with targeted therapies and other oral SERDs in development.
