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ESR1 Mutations
ESR1m emergenceTesting
Efficacy
background
In ER+/HER2- ESR1-mutated mBC following progression on ETEMERALD comprised patients with real-world characteristics including 100% prior CDK4/6i exposure and high disease burden1,2

A GLOBAL, PROSPECTIVE, RANDOMIZED, OPEN-LABEL  PHASE 3 TRIAL1,3


ESR1-mutated mBC study
population (n=228)1*

  • Postmenopausal women and men
  • ER+/HER2- advanced or metastatic breast cancer
  • Progression on 1-2 lines of ET, at least one in combination with a CDK4/6i
  • ≤1 line of chemotherapy for advanced or metastatic disease
  • ECOG PS 0 or 1
Stratification factors:presence of visceral metastases, previous fulvestrant use1

Randomized 1:1

ORSERDU 345 mg (n=115)1

Progressive disease or unacceptable toxicity

Endocrine monotherapy of
investigator's choice (n=113)1

Fulvestrant, anastrozole, letrozole, or exemestane

Progressive disease or unacceptable toxicity

Primary endpoint

  • PFS in the ESR1-mutated mBC population1†
    • Median PFS
Prespecified landmark
PFS assessments2:

3 months, 6 months,
12 months, 18 months

CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; ECOG, Eastern Cooperative Oncology Group; 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; PS, performance status.

*This global phase 3 trial included patients with and without identified ESR1 mutations (N=478). Results presented within are from the ESR1-mutated mBC population only.1,3

PFS was assessed by an independent blinded imaging review committee.1


In ER+/HER2- ESR1-mutated mBC following progression on ETBaseline characteristics were consistent with patients commonly seen in clinical practice3Select baseline characteristics in the ORSERDU arm

100%

70%

~70%

~64%

of patientsof patientsof patientsof patients

received a prior
CDK4/6i1

had visceral metastases,
majority were liver (52%)
and/or lung (24%)2

were on a prior
CDK4/6i for
12 months or more4

had 1 prior line of ET
in the advanced or
metastatic setting3

BASELINE CHARACTERISTICS3

ORSERDUSOC endocrine monotherapy*
ParameterESR1-mutated mBC (n=115)ESR1-mutated mBC (n=113)

Median age, years (range)

64 (28-89)63 (32-83)

Race or ethnicity

White89.4%87.0%
Asian5.3%8.7%
Hispanic8.7%8.8%
Black or African American4.3%4.3%
Other/unknown1.1%0%

ECOG PS

058.3%54.9%
141.7%45.1%

Visceral metastases

70.4%74.3%

Prior adjuvant therapy

53.9%57.5%

Prior CDK4/6i

100%100%

Prior lines of ET in advanced or metastatic setting

163.5%61.1%
236.5%38.9%

Prior lines of chemotherapy in advanced or metastatic setting

077.4%71.7%
122.6%28.3%

Any prior ET

97.4%96.5%
Fulvestrant23.5%24.8%
Al87.8%85.0%

AI, aromatase inhibitor; CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; ECOG, Eastern Cooperative Oncology Group; ER+, estrogen receptor-positive; ESR1, estrogen receptor 1; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; mBC, metastatic breast cancer; PS, performance status; SOC, standard of care.

*SOC endocrine monotherapy included either fulvestrant, anastrozole, letrozole, or exemestane.1

Includes lung, liver, brain, pleural, and peritoneal involvement.3


In ER+/HER2- ESR1-mutated mBC following progression on ETORSERDU: 2x mPFS vs SOC in EMERALD, in which all patients were previously treated with a CDK4/6i + ET1*

PRIMARY ENDPOINT IN EMERALD: PFS IN PATIENTS WITH ESR1-MUTATED mBC1

PFS in Patients Taking ORSERDU™ (elacestrant) vs SOC Endocrine Monotherapy
  • Absolute difference in mPFS of 1.9 months between SOC and ORSERDU arms1

  • In EMERALD, 73% in the SOC arm were treated with fulvestrant3

  • In a post hoc analysis, patients on fulvestrant achieved 1.9 months mPFS, while patients on ORSERDU achieved 3.8 months3

  • Post hoc analysis data are observational in nature. There was no prespecified statistical procedure controlling for type 1 error.

  • Due to low bioavailability, fulvestrant is only available as an IM injection5,6

  • Fulvestrant is not indicated to treat ESR1-mutated disease5

CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; CI, confidence interval; ER+, estrogen receptor-positive; ESR1, estrogen receptor 1; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR, hazard ratio; IM, intramuscular; mBC, metastatic breast cancer; mPFS, median progression-free survival; PFS, progression-free survival; SOC, standard of care.

*mPFS was the primary endpoint. SOC endocrine monotherapy included either fulvestrant, anastrozole, letrozole, or exemestane.1

95% CI: 2.2-7.3.1

95% CI: 1.9-2.1.1

About endpoints

Selected 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.

Please see additional Important Safety Information below. Please see full Prescribing Information.


In ER+/HER2- ESR1-mutated mBC following progression on ETPost hoc analysis: ORSERDU showed longer mPFS for patients previously treated with a CDK4/6i + ET for 12 months or more vs SOC4*

POST HOC ANALYSIS: mPFS IN PATIENTS WITH ≥12 MONTHS PRIOR CDK4/6i + ET4

mPFS in Patients Taking ORSERDU™ (elacestrant) vs SOC Endocrine Monotherapy
  • Absolute difference in mPFS of 6.7 months between SOC and ORSERDU arms4

SEPARATE POST HOC ANALYSIS:
mPFS IN SUBGROUPS OF PATIENTS WITH ≥12 MONTHS PRIOR CDK4/6i10

Patients

% (n)

ORSERDU

SOC endocrine monotherapy

HR (95% CI)

ESR1m and bone metastasesII

86 (136)

9.13 (5.49-16.89)

1.91 (1.87-3.71)

0.38 (0.230-0.623)

ESR1m and liver and/or lung metastases

71 (113)

7.26 (2.20-10.84)

1.87 (1.84-1.94)

0.35 (0.209-0.589)

ESR1m and PIK3CAm#

39 (62)

5.45 (2.14-10.84)

1.94 (1.84-3.94)

0.42 (0.176-0.941)

ESR1m and HER2-low expression**

48 (77)

9.03 (5.49-16.89)

1.87 (1.84-3.75)

0.30 (0.142-0.604)

ESR1m and TP53m

38 (61)

8.61 (3.65-24.25)

1.87 (1.84-3.52)

0.30 (0.132-0.643)

The results of these post hoc analyses of mPFS by duration of CDK4/6i are observational in nature and should be interpreted with caution. There was no prespecified statistical procedure controlling for type 1 error. ORSERDU is NOT indicated to target PIK3CA or TP53 mutations.

CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; CI, confidence interval; ER+, estrogen receptor-positive; ESR1, estrogen receptor 1; ESR1m, estrogen receptor 1 mutation; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR, hazard ratio; IHC, immunohistochemistry; ISH, in situ hybridization; mBC, metastatic breast cancer; mPFS, median progression-free survival; PFS, progression-free survival; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; SOC, standard of care.

*Post hoc analysis of mPFS results in the EMERALD trial based on duration of prior CDK4/6i usage. SOC endocrine monotherapy included either fulvestrant, anastrozole, letrozole, or exemestane.1 ‡95% CI: 4.1-10.8.4 §95% CI: 1.9-3.7.4 II85% of patients had bone and other sites of metastases (30% of these patients had no liver or lung involvement).10 55% of patients had liver and other sites of metastases (10% of these patients had no lung or bone involvement); 25% of patients had lung and other sites of metastases (2% of these patients had no liver or bone involvement).10 #Includes E545K, H1047R, E542K among others.10 **HER2 IHC 1+, and 2+ with no ISH amplification. Data not available for all patients.10

Learn more about Safety

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. ORSERDU [prescribing information]. New York, NY: Stemline Therapeutics, Inc., a Menarini Group Company, 2023. 2. Data on file. Stemline Therapeutics, Inc., a Menarini Group Company. 3. 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. 4. Bardia A, Bidard FC, Neven P, et al. EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+/HER2- metastatic breast cancer: updated results by duration of prior CDK4/6i in metastatic setting. Presented at: San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. 5. Faslodex [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 6. Robertson JFR, Harrison M. Fulvestrant: pharmacokinetics and pharmacology. Br J Cancer. 2004;90(suppl 1):S7-S10. 7. NCI Dictionary of Cancer Terms. PFS. Accessed January 14, 2023. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/pfs. 8. NCI Dictionary of Cancer Terms. Median survival. Accessed January 14, 2023. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/median-survival. 9. Kok PS, Cho D, Yoon WH, et al. Validation of progression-free survival rate at 6 months and objective response for estimating overall survival in immune checkpoint inhibitor trials: a systematic review and meta-analysis. JAMA Netw Open. 2020;3(9):e2011809. 10. Bardia A, O’Shaughnessy J, Bidard FC, et al. Elacestrant vs standard-of-care in ER+/HER2- advanced or metastatic breast cancer (mBC) with ESR1 mutation: key biomarkers and clinical subgroup analyses from the phase 3 EMERALD trial. Presented at: San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX.

ORSERDU is a registered trademark of the Menarini Group.

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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. ORSERDU [prescribing information]. New York, NY: Stemline Therapeutics, Inc., a Menarini Group Company, 2023. 2. Data on file. Stemline Therapeutics, Inc., a Menarini Group Company. 3. 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. 4. Bardia A, Bidard FC, Neven P, et al. EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+/HER2- metastatic breast cancer: updated results by duration of prior CDK4/6i in metastatic setting. Presented at: San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. 5. Faslodex [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 6. Robertson JFR, Harrison M. Fulvestrant: pharmacokinetics and pharmacology. Br J Cancer. 2004;90(suppl 1):S7-S10. 7. NCI Dictionary of Cancer Terms. PFS. Accessed January 14, 2023. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/pfs. 8. NCI Dictionary of Cancer Terms. Median survival. Accessed January 14, 2023. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/median-survival. 9. Kok PS, Cho D, Yoon WH, et al. Validation of progression-free survival rate at 6 months and objective response for estimating overall survival in immune checkpoint inhibitor trials: a systematic review and meta-analysis. JAMA Netw Open. 2020;3(9):e2011809. 10. Bardia A, O’Shaughnessy J, Bidard FC, et al. Elacestrant vs standard-of-care in ER+/HER2- advanced or metastatic breast cancer (mBC) with ESR1 mutation: key biomarkers and clinical subgroup analyses from the phase 3 EMERALD trial. Presented at: San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX.