The Menarini Group (Menarini) and Stemline Therapeutics (Stemline) announced results from a new analysis of the pivotal EMERALD clinical study that suggest that oral single-agent elacestrant may be effective in ER+, HER2- advanced or metastatic breast cancer patients with Non-Detected ESR1-mut whose disease has progressed within six months of treatment with a CDK4/6i. Results from this new post-hoc subgroup analysis will be presented at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL. EMERALD is a Phase 3 registrational trial that demonstrated statistically significant PFS with elacestrant versus SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane).

Based on these results, the U.S. Food & Drug Administration (FDA) approved ORSERDU (elacestrant) on January 27, 2023, for the treatment of postmenopausal women or adult men with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. ESR1 mutations are present in up to 40% of ER+, HER2- advanced or metastatic breast cancers, and they are a known driver of resistance to standard endocrine therapy. Importantly, a previous subgroup analysis of the EMERALD PFS results, which were presented at the San Antonio Breast Cancer Symposium (SABCS) 2022, demonstrated that the duration of prior CDK4/6i treatment was positively associated with longer PFS on elacestrant but not with SOC.

For patients with ESR1-mut who were treated with CDK4/6i for =12 months prior to randomization on EMERALD, elacestrant achieved a median PFS of 8.6 months versus 1.9 months on SOC, with an absolute difference of 6.7 months, and a 59% reduction in the risk of progression or death (HR=0.41 95% CI: 0.26-0.63). In this new analysis to be presented at ASCO 2023, researchers evaluated treatment with elacestrant in a subgroup of patients with Non-Detected ESR1-mut enrolled in the EMERALD study with rapidly progressing disease. Results for patients whose disease progressed within six months of CDK4/6i therapy demonstrated a median PFS of 5.32 months for the elacestrant arm, compared to 1.87 months for patients who received SOC (HR 0.518; 95% CI: 0.216-1.165).

Safety data were consistent with previously reported results. Most adverse events (AEs), including nausea, were grade 1 and 2, and no grade 4 treatment-related AEs (TRAEs) were reported. Only 3.4% of patients receiving elacestrant and 0.9% receiving SOC discontinued therapy due to any TRAE.

No deaths assessed as treatment-related were reported in either arm. No hematologic safety signal was observed, and none of the patients in either treatment arm had sinus bradycardia.