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.

Treatment with elacestrant was associated with prolonged PFS at 6, 12, 15, and 18 months compared to fulvestrant or AI in both the overall population and pts with mESR1...Among pts with ER+/HER2− mBC, elacestrant prolonged PFS compared to both fulvestrant as well as AI, highlighting superior efficacy regardless of type of endocrine therapy.

The Menarini Group...and Stemline Therapeutics (“Stemline”)...announced that the U.S. Food and Drug Administration (FDA) has accepted the Company’s New Drug Application (NDA) for elacestrant, an investigational selective estrogen receptor degrader (SERD), for patients with ER+/HER2- advanced or metastatic breast cancer. The FDA has granted the application Priority Review...EMERALD met both of its pre-specified primary endpoints of progression-free survival (PFS) in the overall population and in patients with the ESR1 mutation (mESR1)...

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.

In the phase III EMERALD trial, the investigational oral selective estrogen receptor degrader elacestrant offered a modest but statistically significant improvement in progression-free survival in patients with ER-positive/HER2-negative breast cancer previously treated with endocrine therapy and a CDK4/6 inhibitor.

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...

...Patient must have ER positive, HER-2 negative tumor status as confirmed by local laboratory testing either from a fresh biopsy or from an archival tissue obtained no more than 2 years prior to signing of the informed consent form. ...

...- Histologically confirmed diagnosis of ER-positive, HER2-negative locally advanced or metastatic breast cancer....

......

...ER-positive with expression higher than 10% and HER2-negative tumor...

...- Female or male patients with histologically confirmed ER positive (regardless of PR), HER2 negative breast cancer, according to local pathologist:...

In untreated ER+/HER2-negative early BC a short-course preoperative treatment with elacestrant was associated with relevant biological and molecular response and with manageable safety profile.