Comparative Trial Features of Oral SERDs and Combination Approaches in HR Positive Breast Cancer

This segment parses key distinctions across pivotal oral SERD trials to guide clinical interpretation and sequencing. Panelists highlight that EMERALD enrolled a more heavily pretreated cohort with near universal prior CDK4/6 exposure and allowed prior chemotherapy, concentrating benefit in patients with ESR1 mutations and longer prior endocrine sensitivity. EMBER-3 employed a staged design that required demonstration of single agent activity before progressing to combination assessment and included a higher proportion of patients without prior CDK4/6 exposure, which affects cross trial comparability. For combination development, ELEVATE and EvERA pair SERDs with mTOR pathway inhibition and other targeted agents to overcome endocrine resistance. These combination trials show signals of increased activity but introduce overlapping toxicities such as stomatitis, fatigue and metabolic effects that necessitate prophylaxis and closer monitoring. Clinicians therefore interpret efficacy within the context of prior therapy, ESR1 mutation enrichment, and tolerability, using those parameters to individualize choice between single agent oral SERD and combination strategies.