The Menarini Group...announced today that the European Commission has approved ORSERDU® (elacestrant) as a monotherapy for the treatment of postmenopausal women, and men, with estrogen receptor (ER)‑positive, HER2-negative, locally advanced or metastatic breast cancer (mBC) with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy including a CDK 4/6 inhibitor....The approval of ORSERDU is supported by data from the Phase 3 EMERALD trial, which demonstrated statistically significant progression-free survival (PFS) with elacestrant versus standard-of-care (SOC), defined as investigator’s choice of an approved endocrine monotherapy.

On January 27, 2023, the Food and Drug Administration (FDA) approved elacestrant (Orserdu, Stemline Therapeutics, Inc.) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. FDA also approved the Guardant360 CDx assay as a companion diagnostic device to identify patients with breast cancer for treatment with elacestrant.

The Menarini Group (“Menarini”)...announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion on the approval of ORSERDU® (elacestrant) monotherapy, indicated for the treatment of postmenopausal women, and men, with estrogen receptor (ER)‑positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy including a CDK 4/6 inhibitor.

EMERALD (NCT03778931) is a randomized, open-label, phase 3 trial that enrolled pts with ER+/HER2- MBC ....Patients were randomized 1:1 to elacestrant (400 mg orally daily) or SoC....Updated PFS results show statistically significant results in favor of elacestrant, both in all pts and in pts with ESR1-mut....Elacestrant demonstrated longer PFS versus SOC that was positively associated with the duration of prior treatment with CDK4/6i, which was more pronounced in pts with ESR1-mut MBC. In this 2nd and 3rd line setting, elacestrant was well tolerated with significantly longer PFS versus SoC, highlighting its potential role as a therapeutic option for pts with ER+/HER2- MBC.

Among patients without prior chemotherapy, treatment with elacestrant was associated with significantly prolonged PFS compared to SOC in both the overall population (hazard ratio [HR] = 0.68 [95% CI, 0.52-0.89] P = 0.004; median PFS 3.7 vs 2.0; 6-mo PFS 38% vs 23%; 12-mo PFS 27% vs 12%), and patients with mESR1 (HR = 0.54 [95% CI, 0.36-0.80] P = 0.002; median PFS 5.3 vs 1.9; 6-mo PFS 44% vs 24%; 12-mo PFS 31% vs 12%)...Among patients with ER+/HER2− mBC without prior chemotherapy, elacestrant significantly prolonged PFS compared to SOC endocrine therapy and showed favorable outcomes in this subgroup.

PFS was prolonged in all patients (hazard ratio = 0.70; 95% CI, 0.55 to 0.88; P = .002) and patients with ESR1 mutation (hazard ratio = 0.55; 95% CI, 0.39 to 0.77; P = .0005)….Elacestrant is the first oral selective ER degrader demonstrating a significant PFS improvement versus SOC both in the overall population and in patients with ESR1 mutations with manageable safety in a phase III trial for patients with ER-positive/HER2-negative advanced breast cancer.

The study was designed to evaluate elacestrant as a monotherapy versus the standard of care (SoC) for the treatment of ER+/HER2- advanced or metastatic breast cancer (mBC)…EMERALD met both primary endpoints, showing statistically significant PFS in the overall population and ESR1 mutation subgroup...Overall, 466 patients were enrolled in the study, including 220 (47%) with tumors harboring an Estrogen Receptor 1 (ESR1) mutation...

A clinically meaningful improvement in PFS favoring elacestrant compared to SOC was consistent across all relevant subgroups in pts with ESR1-mut….Elacestrant showed significantly greater PFS when prior treatment duration with CDK4/6i was at least 12 months, suggesting prior exposure to CDK4/6i is a surrogate marker for endocrine sensitivity.

This phase I study (RAD1901-005; NCT02338349) evaluated elacestrant, an investigational oral selective estrogen receptor degrader (SERD), in heavily pretreated women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer, including those with estrogen receptor gene alpha (ESR1) mutation....The objective response rate was 19.4% (n = 31 evaluable patients receiving RP2D), 15.0% in patients with prior SERD, 16.7% in patients with prior CDK4/6i, and 33.3% in patients with ESR1 mutation (n = 5/15).