Elacestrant ups PFS vs SoC ET in ER-positive, HER2-negative advanced breast cancer

Elacestrant, a novel oral selective oestrogen receptor (ER) degrader, significantly improves progression-free survival (PFS) vs standard-of-care (SoC) endocrine therapy (ET) in patients with ER-positive, HER2-negative advanced breast cancer whose disease progressed after 1–2 prior lines of ET and a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, results of the phase III EMERALD trial have shown.

“Among these patients, 43.4 percent of whom had received two prior lines of ET, elacestrant significantly reduced the risk of disease progression or death vs SoC by 30 percent in the overall cohort and by 45 percent in patients with ESR1 mutation,” the investigators highlighted. [J Clin Oncol 2022;doi:10.1200/JCO.22.00338]

The multicentre, open-label study included 477 patients (median age, 63 years; detectable ESR1 mutation, 47.8 percent) with ER-positive, HER2-negative advanced or metastatic breast cancer whose disease progressed after first- or second-line treatment with ET in combination with a CDK4/6 inhibitor. In the advanced or metastatic disease setting, 43.4 percent of the patients had received two prior lines of ET, while 22.2 percent had received one prior chemotherapy regimen.

The patients were randomized 1:1 to receive elacestrant (400 mg QD orally; dose reductions to 200 mg or 300 mg daily permitted for toxicity) (n=239) or investigator’s choice of SoC ET with fulvestrant, anastrozole, letrozole or exemestane monotherapy (n=238). Baseline characteristics were well balanced between the treatment groups, with visceral metastasis present in a majority of patients in each group (68.2 percent in the elacestrant group vs 71 percent in the SoC ET group).

After a median follow-up of 15.1 months, PFS was significantly improved with elacestrant vs SoC ET in all patients (hazard ratio [HR], 0.70; 95 percent confidence interval [CI], 0.55–0.88; p=0.002) and in patients with ESR1 mutation (HR, 0.55; 95 percent CI, 0.39–0.77; p=0.0005). PFS rates at 6 months and 12 months were 34.3 percent vs 20.4 percent and 22.3 percent vs 9.4 percent, respectively, in the overall population. In patients with ESR1 mutation, 6-month and 12-month PFS rates were 40.8 percent vs 19.1 percent and 26.8 percent vs 8.2 percent, respectively.

“The efficacy of elacestrant was maintained when compared with the fulvestrant subgroup in secondary analysis,” the investigators noted. In the overall population, the PFS HR was 0.68 (95 percent CI, 0.52–0.90; p=0.0049) for elacestrant vs fulvestrant, with 6-month and 12-month PFS rates of 34.3 percent vs 22.9 percent and 22.3 percent vs 10.2 percent, respectively. In patients with ESR1 mutation, the PFS HR was 0.50 (95 percent CI, 0.34–0.74; p=0.0005), with 6-month and 12-month PFS rates of 40.8 percent vs 20.8 percent and 26.8 percent vs 8.4 percent, respectively.

In the study, treatment-related grade 3/4 adverse events (TRAEs) occurred in 7.2 percent vs 3.1 percent of patients in the elacestrant vs SoC ET group. TRAEs led to treatment discontinuation in 3.4 percent vs 0.9 percent of the patients. The most common grade 3/4 AEs in the elacestrant group were nausea (2.5 percent vs 0.9 percent for SoC ET), back pain (2.5 percent vs 0.4 percent), and increased alanine transaminase (2.1 percent vs 0.4 percent).

“Elacestrant is the first oral selective ER degrader demonstrating a significant improvement in PFS vs SoC ET in both the overall population and in patients with ESR1 mutation in a phase III trial of patients with ER-positive, HER2-negative advanced breast cancer, with a manageable safety profile,” the investigators concluded. “These data represent an opportunity to potentially offer a new oral ET option to patients with previously treated, metastatic, hormone receptor–positive breast cancer, including ESR1-mutant breast cancer.”