Elacestrant (Orserdu®): A Comprehensive Clinical and Regulatory Monograph on the First-in-Class Oral SERD for ESR1-Mutated ER+/HER2- Metastatic Breast Cancer

Executive Summary

[Elacestrant, marketed under the brand name Orserdu®, represents a significant therapeutic advance in the management of hormone-driven breast cancer. It is a first-in-class, orally bioavailable selective estrogen receptor degrader (SERD) that has secured regulatory approval for the treatment of postmenopausal women and adult men with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (][ESR1][)-mutated advanced or metastatic breast cancer that has progressed following at least one line of endocrine therapy.][1]

[The foundation of its approval rests on the pivotal Phase 3 EMERALD trial. This study demonstrated that Elacestrant conferred a statistically significant and clinically meaningful improvement in progression-free survival (PFS) when compared directly against standard-of-care (SOC) endocrine monotherapy in its target patient population.][2][ The benefit was most pronounced in patients whose tumors retained a degree of endocrine sensitivity, as evidenced by a longer duration of benefit from prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy.]

[This report provides a comprehensive analysis of Elacestrant, beginning with its unique pharmacological profile and dual mechanism of action that enables it to overcome acquired resistance driven by ][ESR1][ mutations. It critically examines the clinical evidence from the EMERALD trial, including key subgroup analyses that are essential for optimal patient selection. A detailed overview of the drug's safety, tolerability, and management of adverse events is presented, alongside a summary of its global regulatory journey with the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and other health authorities.]