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The Menarini Group presents at SABCS 2023 new progression-free survival data from the EMERALD clinical study of ORSERDU® (elacestrant) in clinically relevant subgroups of patients with ER, HER2- metastatic breast cancer (MBC) with ESR1 mutations
• This new post hoc analysis of the Phase 3 EMERALD trial evaluated elacestrant in the endocrine-sensitive population (CDK4/6 inhibitor duration of at least 12 months) with tumors harboring ESR1 mutations.
• This analysis shows a clinically significant improvement in progression-free survival in all subgroups studied, including those patients with bone, liver and/or lung metastases, those with common concomitant mutations such as PIK3CA and TP53, as well as those with low expression of HER2.
• These results demonstrate that when tumors with ESR1 mutations remain sensitive to the endocrine system, the ER pathway could be a key driver of the disease.
FLORENCE, Italy and NEW YORK, December 11, 2023 /PRNewswire/ -- The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a subsidiary 100% of the Menarini Group, focused on offering transformative oncology treatments to cancer patients, today presented the results of a new post hoc analysis of the EMERALD pivotal clinical study that demonstrates a clinically significant improvement in progression-free survival (PFS) in all relevant subgroups. Data show favorable PFS of ORSERDU® (elacestrant) as a single agent compared to standard of care (SOC) in patients with ER, HER2- advanced or metastatic breast cancer (MBC) with tumors sensitive to endocrine drugs and who harbor ESR1 mutations, when the duration of prior treatment with CDK4/6 inhibitors was at least 12 months. These data will be presented at the 2023 San Antonio Breast Cancer Symposium (SABCS), which will be held December 5-9, 2023.
EMERALD is a phase 3 registration trial that demonstrated statistically significant PFS with ORSERDU versus endocrine monotherapy with SOC (fulvestrant, letrozole, anastrozole, exemestane). Based on these results, the FDA approved ORSERDU on January 27, 2023 for the treatment of postmenopausal women or adult men with advanced or metastatic ER, HER2-, ESR1-mutated breast cancer with disease progression after at least one line of therapy. endocrine. Mutations in ESR1 are present in up to 40% of cases of ER, HER2- advanced or metastatic breast cancer. They are a known resistance factor to standard endocrine therapy and, until now, tumors harboring these mutations have been more difficult to treat.
Importantly, a previous post hoc subgroup analysis of EMERALD PFS outcomes, presented at SABCS 2022, demonstrated that duration of prior treatment with CDK4/6 inhibitors was positively associated with longer PFS with ORSERDU , but not with SOC. For patients with ESR1 mutations who were treated with CDK4/6 inhibitors for at least 12 months before randomization in EMERALD, ORSERDU achieved a median PFS of 8.6 months versus 1.9 months with SOC, with a 59% reduction in the risk of progression or death (HR=0.41 95% CI: 0.26-0.63). [1]
In this updated analysis, Menarini Stemline evaluated the benefit of single-agent ORSERDU in high-prevalence clinical and key biomarker subgroups, including patients with bone, liver, and/or lung metastases; those with common concomitant mutations in PIK3CA or TP53; or those with low HER2 expression.
"These updated results further reinforce that ORSERDU monotherapy is a promising second-line treatment option for patients with ER, HER2- metastatic breast cancer whose tumors harbor ESR1 mutations," explained Virginia Kaklamani, MD, DSc, medical oncologist at mom and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center. "We have observed consistent improvements over standard treatment in progression-free survival in many important subgroups with elacestrant monotherapy for patients whose duration of prior treatment with CDK 4/6 was at least 12 months. We have observed these results not only in metastases bone, but also in liver and/or lung metastases, and in patients with common mutations such as PIK3CA and TP53, and in patients with low HER2 expression.
ORSERDU demonstrated a clinically significant improvement in PFS, compared to endocrine monotherapy with SOC (fulvestrant, letrozole, anastrozole, exemestane), in all of these subgroups. ORSERDU showed significantly longer PFS when the duration of prior treatment with CDK4/6 inhibitors was at least 12 months, indicating that when ESR1 mutated tumors remain endocrine sensitive, the ER pathway could be a key driver of disease, regardless of metastatic site, concomitant PIK3CA or TP53 mutations, or low HER2 expression. The full summary can be found here.
"The data presented here at SABCS 2023 builds on our body of knowledge about ORSERDU and its potential as a single-agent therapy targeting tumors with ESR1 mutations," said Elcin Barker Ergun, CEO of the Menarini Group. "At Menarini Stemline our goal is to provide transformative treatments that help prolong and improve the lives of people suffering from cancer. We are proud to offer a much-needed endocrine option for a multitude of patients with metastatic breast cancer, and one that also has a manageable security profile".
Safety data were consistent with previously reported results. The most common adverse reactions with ORSERDU were musculoskeletal pain, nausea, increased triglycerides, increased cholesterol, vomiting, fatigue, dyspepsia, diarrhea, decreased calcium, back pain, increased creatinine, arthralgia, decreased sodium, constipation , headache, hot flashes, abdominal pain, anemia, decreased potassium and increased alanine aminotransferase. Below is important information about the safety of ORSERDU.
See details of all Menarini Group/Stemline Therapeutics presentations at SABCS 2023 here.
About the Phase 3 EMERALD Study (NCT03778931)The Phase 3 EMERALD trial is a randomized, open-label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in patients with CMB/more advanced ER and HER2-. The study included 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK4/6 inhibitor. Study patients were randomly assigned to one or two lines of endocrine therapy. Study patients were randomized to receive elacestrant or the approved hormonal agent chosen by the investigator. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with mutations in the estrogen receptor 1 (ESR1) gene. In the group of patients whose tumors had ESR1 gene mutations, elacestrant achieved a median PFS of 3.8 months versus 1.9 months with SOC, and reduced the risk of progression or death by 45% (HR PFS= 0.55, 95% CI: 0.39, 0.77) versus SOC.
About ORSERDU (elacestrant) Indication for the United States: ORSERDU (elacestrant), 345 mg tablets, is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, estrogen receptor (ER)-negative advanced or metastatic breast cancer. human epidermal growth factor receptor 2 (HER2), with ESR1 mutation and disease progression after at least one line of endocrine treatment.
Complete US prescribing information available at www.orserdu.com.
Important Safety Information Warning and Precautions
Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU with an incidence of 30% and 27%, respectively. The incidence of grade 3 and 4 hypercholesterolemia and hypertriglyceridemia was 0.9% and 2.2%, respectively. Monitor lipid profile before starting and periodically while taking ORSERDU. Embryo-fetal toxicity: Based on findings in animals and its mechanism of action, ORSERDU may cause fetal harm when administered to a pregnant woman. Counsel pregnant women and women of reproductive potential about the potential risk to the fetus. Advise women of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive age to use effective contraception during treatment with ORSERDU and for 1 week after the last dose.
Adverse reactions
Serious adverse reactions occurred in 12% of patients receiving ORSERDU. Serious adverse reactions in >1% of patients receiving ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients receiving ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient in each case). The most common adverse reactions (>10%), including Laboratory abnormalities from ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite (15%), diarrhea (13%), headache (12%), constipation (12%), abdominal pain (11%), hot flashes (11%) and dyspepsia (10%).
Drug interactions
Concomitant use with CYP3A4 inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.
Use in specific populations
Breast-feeding: Advise breast-feeding women not to breast-feed during treatment with ORSERDU and for 1 week after the last dose. Liver Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B). The safety and effectiveness of ORSERDU in pediatric patients have not been established.
To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
About the Elacestrant Clinical Development Program Elacestrant is also being investigated in several clinical trials in metastatic breast cancer disease, alone or in combination with other therapies. ELEVATE ( NCT05563220) is a Phase 1b/2 clinical trial that will evaluate the safety and efficacy of elacestrant combined with alpelisib, everolimus, palbociclib, abemaciclib, and ribociclib. ELECTRA (NCT05386108) is an open-label, multicenter, phase 1b/2 study evaluating elacestrant in combination with abemaciclib in patients with ER, HER2- breast cancer. The phase 2 portion evaluates this treatment regimen in this population of patients with brain metastases. ELCIN (NCT05596409) is a phase 2 trial evaluating the efficacy of elacestrant in patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer who received a or two prior hormonal therapies and no CDK4 and CDK6 enzyme inhibitor (CDK4/6i) targeting cyclin-dependent kinase in the metastatic setting. Elacestrant is also being evaluated in early breast cancer.
About the Menarini GroupThe Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of more than $4.4 billion and more than 17,000 employees. Menarini focuses on therapeutic areas with high unmet needs, with products for cardiology, oncology, pulmonology, gastroenterology, infectious diseases, diabetology, inflammation and analgesia. With 18 production plants and 9 Research and Development centers, Menarini products are available in 140 countries around the world. For more information, visit www.menarini.com.
About Stemline Therapeutics Inc.Stemline Therapeutics, Inc. ("Stemline"), a wholly owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapies. Stemline markets ORSERDU® (elacestrant) in the United States and the EU, an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men who are estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative, advanced or metastatic breast cancer with ESR1 mutation and disease progression after at least one line of endocrine therapy. Stemline also markets ELZONRIS® (tagraxofusp-erzs), a novel CD123-targeted treatment for patients with blastoid plasmacytoid dendritic cell neoplasia (BPDCN), an aggressive hematologic cancer, in the United States and Europe, which is the only approved treatment for BPDCN in the United States and the EU to date. Stemline also markets NEXPOVIO® (selinexor), an XPO1 inhibitor for multiple myeloma, in Europe. Stemline also has a broad portfolio of small molecules and biologics in various phases of development for a number of solid and hematologic cancers.
[1] Bardia et al. EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER/HER2- metastatic breast cancer: Results updated according to the duration of previous treatment with CDK4/6i in the metastatic context. SABCS 2022. GS3-01
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