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Emerald Study: Menarini's Orserdu Offers Hope for ER+ Breast Cancer Patients


8 December 2023

Menarini Group has announced promising results from the EMERALD Clinical Study, presented at SABCS 2023. The trial demonstrates that Orserdu provides substantial improvements in progression-free survival for metastatic breast cancer patients with ER+, HER2-negative tumors carrying ESR1 mutations.

This Phase 3 clinical study, jointly presented by the Menarini Group and Stemline Therapeutics at the 2023 San Antonio Breast Cancer Symposium (SABCS23), underscores Orserdu®'s (elacestrant) potential as a game-changing therapy for ER+ metastatic breast cancer patients with ESR1 mutations. The research highlights its promise as a second-line treatment option for those with estrogen receptor-positive (ER+), HER2-negative tumors that harbor ESR1 mutations.

Professor Virginia Kaklamani, a breast medical oncologist at UT HSA, MD Anderson Cancer Center, emphasized the consistent improvements seen across numerous subgroups, stating, 

“These updated findings further reinforce that monotherapy ORSERDU is a promising second-line treatment option for ER+, HER2- patients with metastatic breast cancer whose tumors harbor ESR1 mutations. We’ve seen consistent improvements versus standard of care in progression-free survival across many important subgroups with monotherapy elacestrant for patients whose prior treatment duration with CDK 4/6 was at least 12 months. We’ve observed these results not just for bone metastases, but also for liver and/or lung metastases, and in patients with common co-mutations such as PIK3CA and TP53, and in patients with HER2-low expression.”

The EMERALD Clinical Study

The EMERALD Clinical Study focused on patients with ER+, HER2-negative mBC whose tumors were endocrine-sensitive and carried ESR1 mutations, provided they had undergone at least 12 months of prior treatment with CDK4/6 inhibitors. In a post hoc analysis, ORSERDU demonstrated a substantial improvement in progression-free survival compared to standard-of-care (SOC) treatments like fulvestrant, letrozole, anastrozole, or exemestane. These compelling results led to FDA approval in January 2023, marking a significant milestone in the fight against this challenging form of breast cancer.

Elcin Barker Ergun, CEO of the Menarini Group, underscored their commitment to providing transformational treatments to enhance the lives of cancer patients and stating, “The data presented here at SABCS 2023 build on our body of knowledge on ORSERDU and its potential as a single agent therapy targeting ESR1 mutated tumors. At Menarini Stemline our goal is to provide transformational treatments to help extend and improve the lives of people living with cancer. We are proud to offer a much-needed endocrine option for a multitude of appropriate breast cancer patients, and one that also has a manageable safety profile.”

The Significance of ESR1 Mutations

ESR1 mutations have long posed a significant challenge by promoting resistance to standard endocrine therapy in ER+, HER2-negative mBC. These mutations affect up to 40% of patients, complicating treatment strategies.

However, the EMERALD trial unveiled a positive link between the duration of prior CDK4/6 inhibitor treatment and extended progression-free survival with ORSERDU. Patients with ESR1 mutations who received CDK4/6 inhibitors for at least 12 months before the EMERALD trial achieved a remarkable median progression-free survival of 8.6 months, compared to only 1.9 months with SOC. This marked a substantial 59% reduction in the risk of progression or death (HR=0.41, 95% CI: 0.26-0.63). These findings offer tremendous promise for this challenging patient subgroup.

Safety Profile and Future Prospects

The safety profile of ORSERDU remained consistent with previous reports, with musculoskeletal pain, nausea, and elevated triglycerides being among the most common adverse reactions. This manageable safety profile reinforces ORSERDU's potential as a transformative treatment option.

About the EMERALD Phase 3 Study (NCT03778931)

The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/mBC patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator's choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. In the group of patients whose tumors had ESR1-mutations, elacestrant achieved a median PFS of 3.8 months vs 1.9 months on the SOC, and reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC.


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