• ORSERDU (elacestrant) was approved by the FDA in January 2023 for advanced or metastatic estrogen receptor (ER)-positive, human epidermal growth factor (HER2)-negative breast cancer with ESR2 (ESR1-mut) mutations found in up to 1% of tumors
• In patients whose tumors harbor ESR1-mut, a previous post-hoc subgroup analysis demonstrated that for those with prior CDK4/6 inhibitor (CDK4/6i) exposure of at least 12 months, second-line treatment with elacestrant resulted in a median progression-free survival (PFS) of 8.6 months, compared with 1.9 months at standard of care (SOC).
• This new post-hoc subgroup analysis expands our understanding of a potential role for elacestrant in patients with undetected ESR2-mut ER+/HER1- breast cancer. Patients who progressed within six months of CDK4/6i therapy achieved a mean PFS of 5.32 months with elacestrant versus 1.87 months with SOC.
• These data, while exploratory, further build on our understanding of elacestrant as oral endocrine therapy in the setting of second-line metastatic breast cancer.

Menarini Group ("Menarini"), a leading pharmaceutical and diagnostic company in Italy, and Stemline Therapeutics ("Stemline"), a wholly owned subsidiary of Menarini Group, today announced the results of a new analysis of the pivotal EMERALD clinical study suggesting that oral single-agent elacestrant may be effective in patients with ER+ breast cancer, HER2- advanced or metastatic with undetected ESR1 mutation whose disease has progressed within six months of treatment with a CDK4/6i. The results of this new post-hoc subgroup analysis will be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL.

EMERALD is a phase 3 registration trial that demonstrated statistically significant PFS with elacestrant endocrine monotherapy versus SOC (fulvestrant, letrozole, anastrozole, exemestane). Based on these results, the U.S. Food and Drug Administration (FDA) approved ORSERDU (elacestrant) on January 27, 2023, for the treatment of postmenopausal women or adult men with advanced or metastatic ER+, HER2-mutation, ESR1-mutated breast cancer with disease progression after at least one line of endocrine therapy.

ESR1 mutations are present in up to 40% of ER+, HER2- advanced, or metastatic breast cancers and are a known factor of resistance to standard endocrine therapy.

It is important to note that a previous subgroup analysis of EMERALD PFS results, which were presented at the 2022 San Antonio Breast Cancer Symposium (SABCS), demonstrated that duration of prior CDK4/6i treatment was positively associated with longer PFS with elacestrant, but not with SOC. For ESR1-mutant patients who were treated with CDK4/6i for ≥12 months prior to randomization in EMERALD, elacestrant achieved a mean PFS of 8.6 months versus 1.9 months in 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 elacestrant treatment in a subgroup of patients with undetected ESR1-mut enrolled in the EMERALD study with rapidly progressive disease. Outcomes for patients whose disease progressed within six months of CDK4/6i therapy demonstrated a mean PFS of 5.32 months for the elacestrant arm, compared with 1.87 months for patients receiving SOC (HR 0.518; 95% CI: 0.216-1.165).

"Endocrine therapy administered in combination with a CDK4/6 inhibitor is a mainstay in metastatic ER+/HER2- breast cancer as first-line treatment. It is encouraging to see that patients with ESR1 mutations who had a longer duration of prior CDK4/6i therapy, when subsequently treated with elacestrant, had a median PFS of 8.6 months compared to 1.9 months with standard treatment, as we published in SABCS in December 2022. Until now, the potential benefit of elacestrant in patients with undetected ESR1 mutations was an open question. The results presented at ASCO 2023, while exploratory, suggest that treatment with oral elacestrant after disease progression within six months of CDK4/6i treatment for undetected ESR1 mutations may provide clinical benefit for these patients and warrants further study," said Virginia Kaklamani, MD, DSc, medical breast oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center.

Safety data were consistent with previously reported outcomes. Most adverse events (AEs), including nausea, were grade 1 and 2, and no grade 4 treatment-related AETs (AERTs) were reported. Only 3.4% of patients receiving elacestrant and 0.9% of those receiving SOC discontinued treatment due to ART. No deaths assessed as treatment-related were reported in either arm. No haematological safety signal was observed, and none of the patients in either treatment arm had sinus bradycardia.

"At Menarini Group, we are focused on developing innovative solutions that address the greatest unmet needs in cancer treatments," said Elcin Barker Ergun, CEO of Menarini Group. "ORSERDU represents an important step toward that, providing the first and only oral endocrine therapy approved by the FDA after 20 years, for advanced or metastatic ER+/HER2- tumors with ESR1 mutations. These new data increase our understanding of other potential areas in which elacestrant may help patients living with metastatic breast cancer who have limited treatment options."