The Role of Elacestrant in HR+/HER–- mBC: Insights From the EMERALD Trial

EMERALD Study Foundation for ESR1-Targeted Therapy

The EMERALD study established elacestrant as a landmark treatment in breast oncology for heavily pretreated patients with ESR1 mutations. Study participants had received one to two lines of prior endocrine therapy, often including chemotherapy and fulvestrant in advanced disease settings. The trial compared single-agent elacestrant against standard endocrine therapy, specifically targeting the ESR1 resistance mutation.

In endocrine-sensitive patients who had benefited from prior CDK4/6 inhibitor combinations for over 12 months, elacestrant demonstrated remarkable efficacy. Median progression-free survival reached 8 to 9 months with elacestrant compared to less than 2 months with standard endocrine therapy in patients with ESR1 mutations. This dramatic improvement established elacestrant’s role as a first-in-class medication for this specific resistance mechanism.

ESR1 mutation prevalence increases with treatment lines, affecting 30% to 40% of patients transitioning from first-line therapy and up to 50% of patients moving from second-line to third-line treatment. This progressive accumulation of resistance mutations makes ESR1-targeted therapy increasingly important in later treatment settings. The EMERALD study’s success paved the way for elacestrant’s clinical approval and established the foundation for mutation-directed therapy in breast cancer.