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Tumor biology can change over time as it adapts to selective pressure of prior treatment4
While other mutations are primarily present before mBC diagnosis, ESR1 mutations may develop as a direct result of prior ET treatment, leading to poorer outcomes1,2,5-9
Test for ESR1m at 1L progression to inform her 2L treatment
1L, first line; 2L, second line; AI, aromatase inhibitor; ctDNA, circulating tumor DNA; DNA, deoxyribonucleic acid; ER+, estrogen receptor-positive; ESR1, estrogen receptor 1; ESR1m, estrogen receptor 1 mutation; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; mBC, metastatic breast cancer.
*Higher risk of disease progression for patients with ESR1-mutated, ER+/HER2- 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.7,10-12
†Based on treatment with AI therapy.
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Upon 1L |
Test with liquid |
If ESR1m |
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Test for ESR1m at each progression if not detected previously, as ESR1 mutations may emerge upon repeated exposure to endocrine therapy13,15,16
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Select patients for treatment with ORSERDU based on the presence of an ESR1 mutation in plasma specimen (ctDNA) using an FDA-approved test13
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ctDNA can provide a more complete biomarker profile through liquid biopsy14,17
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Due to their emergent nature, ESR1 mutations are rarely found in primary tumors—testing archival tissue is considered inadequate18
Test for ESR1 mutations. Treat with ORSERDU.
1L, first line; 2L, second line; ctDNA, circulating tumor deoxyribonucleic acid; ER+, estrogen receptor-positive; ESR1, estrogen receptor 1; ESR1m, estrogen receptor 1 mutation; ET, endocrine therapy; FDA, Food and Drug Administration; HER2-, human epidermal growth factor receptor 2-negative; mBC, metastatic breast cancer.
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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.
ORSERDU is available as 345 mg tablets and 86 mg tablets.
INDICATION
ORSERDU (elacestrant) is 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. Zhang K, Hong R, Xu F, et al. Clinical value of circulating ESR1 mutations for patients with metastatic breast cancer: a meta-analysis. Cancer Manag Res. 2018;10:2573-2580. 2. Brett JO, 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. 3. Allouchery V, Beaussire L, Perdrix A, et al. Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients. Breast Cancer Res. 2018;20(1):40. 4. Dustin D, Gu G, Fuqua SAW. ESR1 mutations in breast cancer. Cancer. 2019;125(21):3714-3728. 5. Mankoo PK, Sukumar S, Karchin R. PIK3CA somatic mutations in breast cancer: mechanistic insights from Langevin dynamics simulations. Proteins. 2009;75(2):499-508. 6. Casaubon JT, Kashyap S, Regan JP. BRCA1 and BRCA2 Mutations. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. 7. 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. 8. Arthur LM, Turnbull AK, Renshaw L, et al. Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer. Breast Cancer Res Treat. 2014;147(1):211-219. 9. Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med. 2023;388(22):2058-2070. 10. 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. 11. 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. 12. 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. 13. ORSERDU [prescribing information]. New York, NY: Stemline Therapeutics, Inc., a Menarini Group Company, 2023. 14. 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. 15. Schiavon G, Hrebien S, Garcia-Murillas I, et al. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med. 2015;7(313):313ra182. 16. 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. 17. Lee N, Park MJ, Song W, et al. Currently applied molecular assays for identifying ESR1 mutations in patients with advanced breast cancer. Int J Mol Sci. 2020;21(22):8807. 18. Spoerke JM, Gendreau S, Walter K, et al. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nat Commun. 2016;7:11579.
ORSERDU is a registered trademark of the Menarini Group.
© 2024 Stemline Therapeutics, Inc., a Menarini Group Company. All rights reserved. 10/24 MAT-US-ELA-00146-v4
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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.
ORSERDU is available as 345 mg tablets and 86 mg tablets.
INDICATION
ORSERDU (elacestrant) is 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. Zhang K, Hong R, Xu F, et al. Clinical value of circulating ESR1 mutations for patients with metastatic breast cancer: a meta-analysis. Cancer Manag Res. 2018;10:2573-2580. 2. Brett JO, 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. 3. Allouchery V, Beaussire L, Perdrix A, et al. Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients. Breast Cancer Res. 2018;20(1):40. 4. Dustin D, Gu G, Fuqua SAW. ESR1 mutations in breast cancer. Cancer. 2019;125(21):3714-3728. 5. Mankoo PK, Sukumar S, Karchin R. PIK3CA somatic mutations in breast cancer: mechanistic insights from Langevin dynamics simulations. Proteins. 2009;75(2):499-508. 6. Casaubon JT, Kashyap S, Regan JP. BRCA1 and BRCA2 Mutations. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. 7. 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. 8. Arthur LM, Turnbull AK, Renshaw L, et al. Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer. Breast Cancer Res Treat. 2014;147(1):211-219. 9. Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med. 2023;388(22):2058-2070. 10. 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. 11. 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. 12. 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. 13. ORSERDU [prescribing information]. New York, NY: Stemline Therapeutics, Inc., a Menarini Group Company, 2023. 14. 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. 15. Schiavon G, Hrebien S, Garcia-Murillas I, et al. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med. 2015;7(313):313ra182. 16. 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. 17. Lee N, Park MJ, Song W, et al. Currently applied molecular assays for identifying ESR1 mutations in patients with advanced breast cancer. Int J Mol Sci. 2020;21(22):8807. 18. Spoerke JM, Gendreau S, Walter K, et al. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nat Commun. 2016;7:11579.