Elacestrant in ER+, HER2- metastatic breast cancer with ESR1-mutated tumors: subgroup analysis of the phase III EMERALD trial according to prior duration of endocrine therapy plus CDK4/6 inhibitor and in clinical subgroups.
This subgroup analysis of the phase III EMERALD trial evaluated outcomes in 222 patients with metastatic breast cancer.
Summary
Purpose:
Elacestrant significantly prolonged progression-free survival (PFS) with manageable safety compared to standard endocrine therapy (ET) in patients with estrogen receptor-positive (ER+), HER2-, and estrogen receptor 1-mutated metastatic breast cancer. (ESR1) after endocrine therapy plus cyclin-dependent kinase 4/6 inhibitor (TE+CDK4/6i). In patients with ESR1-mutated tumors, we evaluated the efficacy and safety of elacestrant versus standard therapy based on prior duration of TE+CDK4/6i and in clinical subgroups with TE+CDK4/6i ≥12 months.
Patients and methods:
EMERALD, an open-label phase III trial, randomly assigned patients with ER+, HER2- metastatic breast cancer who had received 1-2 prior lines of TE, mandatory CDK4/6i, and ≤1 chemotherapy to elacestrant (345 mg daily) or standard therapy (aromatase inhibitor or fulvestrant). PFS was assessed in subgroups in post hoc exploratory analyzes without adjustment for multiple testing.
Results:
In patients with ESR1-mutated tumors and TE+CDK4/6i ≥12 months, the median PFS for elacestrant versus standard therapy was 8.6 versus 1.9 months (HR, 0.41; 95% confidence interval, 0.26-0.63) . In this population, the median PFS (in months) for elacestrant versus standard therapy was 9.1 versus 1.9 (bone metastasis), 7.3 versus 1.9 (liver and/or lung metastasis), 9.0 versus 1.9 (
Conclusions:
TE+CDK4/6i prior treatment duration of ≥12 months in metastatic breast cancer was associated with a clinically meaningful improvement in PFS for elacestrant compared with standard treatment and was consistent across all subgroups evaluated in patients with tumors ER+, HER2-, and ESR1 mutations.
