Up to 40% of patients with ER+/HER2- mBC
develop ESR1 mutations after initial endocrine therapy3†
Therapies are needed to address the unmet need for patients with ER+/HER2- ESR1-mutated mBC
1L, first line; AI, aromatase inhibitor; ctDNA, circulating tumor DNA; ER+, estrogen receptor-positive; ESR1, estrogen receptor 1; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; mBC, metastatic breast cancer; PFS, progression-free survival.
*Significantly shorter PFS for patients with ER+/HER2- ESR1-mutated mBC based on data from 4 references: Clatot et al prospectively compared the risk of early progression according to circulating ESR1 mutations, CA-15.3, and cell-free DNA in patients with mBC treated with a 1L AI; Chandarlapaty et al conducted a secondary analysis of a phase 3 clinical trial comparing exemestane with exemestane + everolimus in patients with ER+/HER2- mBC who progressed following a nonsteroidal AI; Turner et al conducted a combined analysis of the phase 3 SoFEA and EFECT trials of fulvestrant vs exemestane to assess the clinical utility of baseline ESR1 ctDNA; Zundelevich et al conducted a retrospective cohort study of 130 archival tumor samples from 103 patients with ER+ breast cancer who were treated with ET prior to local or metastatic recurrence.4-7
†Based on treatment with AI therapy.
 |  |  | |  | |  |
PROGRESSION ON INITIAL | TEST FOR ESR1 | IF ESR1 | PRESCRIBE ORSERDU FOR |
Liquid biopsy is a procedure using blood samples that allows rapid and accurate genotyping8,11
Select patients for treatment with ORSERDU based on the presence of an ESR1 mutation in plasma specimen (ctDNA) using an FDA-approved test10
ESR1-mutated ER+/HER2- mBC is associated with poorer outcomes, so confirming ESR1 mutation status post progression is critical4-7*
CDK4/6i, cyclin-dependent kinase 4/6 inhibitor.
*Significantly shorter PFS for patients with ER+/HER2- ESR1-mutated mBC based on data from 4 references: Clatot et al prospectively compared the risk of early progression according to circulating ESR1 mutations, CA-15.3, and cell-free DNA in patients with mBC treated with a 1L AI; Chandarlapaty et al conducted a secondary analysis of a phase 3 clinical trial comparing exemestane with exemestane + everolimus in patients with ER+/HER2- mBC who progressed following a nonsteroidal AI; Turner et al conducted a combined analysis of the phase 3 SoFEA and EFECT trials of fulvestrant vs exemestane to assess the clinical utility of baseline ESR1 ctDNA; Zundelevich et al conducted a retrospective cohort study of 130 archival tumor samples from 103 patients with ER+ breast cancer who were treated with ET prior to local or metastatic recurrence.4-7
Learn more about ORSERDU Efficacy
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU.
Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females 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 potential 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 who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).
The most common adverse reactions (≥10%), including laboratory abnormalities, of 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 flush (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
Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.
Hepatic 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.
INDICATION
ORSERDU (elacestrant) 345 mg tablets are indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information, including Patient Information.
References: 1. Jeselsohn R, Yelensky R, Buchwalter G, et al. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor–positive breast cancer. Clin Cancer Res. 2014;20(7):1757-1767. 2. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. 2022;40(28):3246-3256. 3. Brett J, Spring LM, Bardia A, Wander SA. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):85. 4. Clatot F, Perdrix A, Beaussire L, et al. Risk of early progression according to circulating ESR1 mutation, CA-15.3 and cfDNA increases under first-line anti-aromatase treatment in metastatic breast cancer. Breast Cancer Res. 2020;22(1):56. 5. Chandarlapaty S, Chen D, He W, et al. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol. 2016;2(10):1310-1315. 6. Turner NC, Swift C, Kilburn L, et al. ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor–positive breast cancer: a combined analysis of the phase III SoFEA and EFECT trials. Clin Cancer Res. 2020;26(19):5172-5177. 7. Zundelevich A, Dadiani M, Kahana-Edwin S, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020;22(1):16. 8. Lee N, Park MJ, Song W, Jeon K, Jeong S. Currently applied molecular assays for identifying ESR1 mutations in patients with advanced breast cancer. Int J Mol Sci. 2020;21(22):8807. 9. Gennari A, André F, Barrios CH, et al; for the ESMO Guidelines Committee. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021;32(12):1475-1495. 10. ORSERDU [prescribing information]. New York, NY: Stemline Therapeutics, Inc., a Menarini Group Company; 2023. 11. Russano M, Napolitano A, Ribelli G, et al. Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples. J Exp Clin Cancer Res. 2020;39(1):95.
ORSERDU is a trademark of the Menarini Group.
© 2023 Stemline Therapeutics, Inc., a Menarini Group Company. All rights reserved. 05/23 ELA-05033v3
|
IMPORTANT SAFETY INFORMATION
+
Warnings and Precautions
Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU.
Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females 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 potential 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 who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).
The most common adverse reactions (≥10%), including laboratory abnormalities, of 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 flush (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
Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.
Hepatic 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.
INDICATION
ORSERDU (elacestrant) 345 mg tablets are indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information, including Patient Information.
References: 1. Jeselsohn R, Yelensky R, Buchwalter G, et al. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor–positive breast cancer. Clin Cancer Res. 2014;20(7):1757-1767. 2. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. 2022;40(28):3246-3256. 3. Brett J, Spring LM, Bardia A, Wander SA. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):85. 4. Clatot F, Perdrix A, Beaussire L, et al. Risk of early progression according to circulating ESR1 mutation, CA-15.3 and cfDNA increases under first-line anti-aromatase treatment in metastatic breast cancer. Breast Cancer Res. 2020;22(1):56. 5. Chandarlapaty S, Chen D, He W, et al. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol. 2016;2(10):1310-1315. 6. Turner NC, Swift C, Kilburn L, et al. ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor–positive breast cancer: a combined analysis of the phase III SoFEA and EFECT trials. Clin Cancer Res. 2020;26(19):5172-5177. 7. Zundelevich A, Dadiani M, Kahana-Edwin S, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020;22(1):16. 8. Lee N, Park MJ, Song W, Jeon K, Jeong S. Currently applied molecular assays for identifying ESR1 mutations in patients with advanced breast cancer. Int J Mol Sci. 2020;21(22):8807. 9. Gennari A, André F, Barrios CH, et al; for the ESMO Guidelines Committee. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021;32(12):1475-1495. 10. ORSERDU [prescribing information]. New York, NY: Stemline Therapeutics, Inc., a Menarini Group Company; 2023. 11. Russano M, Napolitano A, Ribelli G, et al. Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples. J Exp Clin Cancer Res. 2020;39(1):95.