Elacestrant

A randomized, open-label, phase III trial (EMERALD [NCT03778931]) enrolled patients with ER-positive HER2-negative metastatic breast cancer. Eligible patients had previously received one or two lines of endocrine therapy, a CDK4/6 inhibitor, and no more than one line of chemotherapy. A total of 477 patients were randomly assigned in a 1:1 ratio to receive either elacestrant 400 mg orally once daily or standard-of-care endocrine monotherapy. Primary end points were PFS by blinded independent central review in all patients and in patients with detectable ESR1 variants. ESR1 variants were found in 47.8% of patients, and 43.4% of patients had received two prior endocrine therapies. Twenty-nine percent of patients in the elacestrant arm and 31% of patients in the standard-of-care arm had received prior fulvestrant therapy. Less than 5% of patients in either arm had received prior mTOR inhibitor therapy.[34]

A randomized, open-label, phase III trial (EMERALD [NCT03778931]) enrolled patients with ER-positive HER2-negative metastatic breast cancer. Eligible patients had previously received one or two lines of endocrine therapy, a CDK4/6 inhibitor, and no more than one line of chemotherapy. A total of 477 patients were randomly assigned in a 1:1 ratio to receive either elacestrant 400 mg orally once daily or standard-of-care endocrine monotherapy. Primary end points were PFS by blinded independent central review in all patients and in patients with detectable ESR1 variants. ESR1 variants were found in 47.8% of patients, and 43.4% of patients had received two prior endocrine therapies. Twenty-nine percent of patients in the elacestrant arm and 31% of patients in the standard-of-care arm had received prior fulvestrant therapy. Less than 5% of patients in either arm had received prior mTOR inhibitor therapy.[34]

PFS was prolonged in the elacestrant arm in all patients (HR, 0.70; 95% CI, 0.55–0.88; P = .002) and in elacestrant-treated patients with ESR1 variants (HR, 0.55; 95% CI, 0.39–0.77; P = .0005). Among all patients, 6-month PFS rates were 34.3% for patients in the elacestrant arm and 20.4% for patients in the standard-of-care arm. In patients with ESR1 variants, 6-month PFS rates were 40.8% for patients in the elacestrant arm and 19.1% for patients in the standard-of-care arm. Similarly, for all patients, 12-month PFS rates were 22.3% for patients in the elacestrant arm and 9.4% for patients in the standard-of-care arm. For patients with ESR1 variants, 12-month PFS rates were 26.8% for patients in the elacestrant arm and 8.2% for patients in the standard-of-care arm.[34][Level of evidence B1]

A randomized, open-label, phase III trial (EMERALD [NCT03778931]) enrolled patients with ER-positive HER2-negative metastatic breast cancer. Eligible patients had previously received one or two lines of endocrine therapy, a CDK4/6 inhibitor, and no more than one line of chemotherapy. A total of 477 patients were randomly assigned in a 1:1 ratio to receive either elacestrant 400 mg orally once daily or standard-of-care endocrine monotherapy. Primary end points were PFS by blinded independent central review in all patients and in patients with detectable ESR1 variants. ESR1 variants were found in 47.8% of patients, and 43.4% of patients had received two prior endocrine therapies. Twenty-nine percent of patients in the elacestrant arm and 31% of patients in the standard-of-care arm had received prior fulvestrant therapy. Less than 5% of patients in either arm had received prior mTOR inhibitor therapy.[34]

The most common adverse events observed with elacestrant versus standard-of-care therapy included nausea (35.0% vs. 18.8%), fatigue (19.0% vs. 18.8%), vomiting (19.0% vs. 8.3%), decreased appetite (14.8% vs. 9.2%), and arthralgia (14.3% vs. 16.2%). Grade 3 or 4 adverse events occurred in 64 patients (27.0%) who received elacestrant and 47 patients (20.5%) who received standard-of-care therapy. The most common grade 3 or 4 adverse events in the elacestrant arm were nausea (six patients, 2.5%), back pain (six patients, 2.5%), and increased alanine aminotransferase (five patients, 2.1%). The most common grade 3 or 4 adverse events in the standard-of-care arm were nausea, fatigue, diarrhea, and increased aspartate aminotransferase (each occurring in two patients, 0.9%). Adverse events led to treatment discontinuation in 15 patients (6.3%) in the elacestrant arm and 10 patients (4.4%) in the standard-of-care arm.