Advancing Care in ER+/HER2- ESR1m mBC: What EMERALD and Real-World Analyses Tell Us

This content has been sponsored by Stemline Therapeutics, Inc., a Menarini Company Group. MED-05438

Overview

Most patients with ER-positive, HER2-negative metastatic breast cancer receive endocrine therapy plus a CDK4/6 inhibitor as first-line treatment.^1-5 While this is initially effective, most tumors may eventually develop resistance to endocrine therapy—often driven by the development of ESR1 mutations^6,7—which can occur in up to 50% of patients throughout treatment and lead to disease progression.^6,8-12 However, elacestrant, an oral selective estrogen receptor degrader, demonstrated longer median progression-free survival (mPFS; 3.8 months; 95% CI: 2.2–7.3) compared to standard-of-care endocrine therapy (1.9 months; 95% CI: 1.9-2.1) in the Phase III EMERALD trial, particularly in patients with ESR1-mutated tumors.¹³ Among patients treated with elacestrant, nausea was the most frequently reported adverse event, occurring in 35 percent of patients, and was generally mild to moderate in severity.¹³ Treatment discontinuation due to adverse reactions occurred in six percent of patients; dose reductions were reported in three percent, and dose interruptions in 15 percent.¹³ Post hoc analyses of the EMERALD study evaluated mPFS across multiple clinical and genomic subgroups in patients with an ESR1 mutation who received ≥12 months of prior ET +CDK 4/6 inhibitor therapy. Two real-world evidence studies in over 1,000 patients supplementing what was previously reported in the EMERALD study. Joining Dr. Jennifer Caudle to discuss these data is Dr. Seth Wander, an Assistant Professor of Medicine at Harvard Medical School and a medical oncologist at Massachusetts General Hospital.

1. Department of Family Medicine, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, USA
2. Harvard Medical School, Boston, Massachusetts, USA
3. Massachusetts General Hospital, Boston, USA

Dr. Wander has received compensation from Stemline to present the following information on behalf of Stemline.

Highlights of U.S. Prescribing Information

These highlights do not include all the information needed to use elacestrant safely and effectively. See full prescribing information for elacestrant.

Indication and Usage
Elacestrant is an estrogen receptor antagonist indicated for:

• treatment of postmenopausal women or adult men, with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy

Warnings and Precautions

Dislipidemia

• Elacestrant may cause hypercholesterolemia and hypertriglyceridemia. Monitor lipid profile prior to starting treatment and periodically thereafter.

Embryo-Fetal Toxicity

• Elacestrant can cause fetal harm. Advise of the potential risk to a fetus and to use effective contraception.

Adverse Reactions

• The most common (>10%) adverse reactions, including laboratory abnormalities, of elacestrant were musculoskeletal pain, nausea, increased cholesterol, increased AST, increased triglycerides, fatigue, decreased hemoglobin, vomiting, increased ALT, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia.

Drug Interactions

Strong and Moderate CYP3A4 Inducers

• Avoid concomitant use with elacestrant.

Strong and Moderate CYP3A4 Inhibitors

• Avoid concomitant use with elacestrant.

Use in Specific Populations

Lactation

• Advise not to breastfeed.

Hepatic Impairment

• Avoid use in patients with severe hepatic impairment (Child-Pugh C).
• Reduce the dosage for patients with moderate hepatic impairment (Child-Pugh B).

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.

References

1. Burstein HJ et al. Endocrine treatment and targeted therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: ASCO guideline update. J Clin Oncol. 2021;39(35):3959-77.
2. Pfizer Laboratories. Palbociclib Prescribing information. 2025. Available at: https://labeling.pfizer.com/showlabeling.aspx?id=2191. Last accessed: June 16, 2026.
3. Novartis Pharmaceuticals Corporation. Ribociclib Prescribing information. 2025. Available at: https://www.novartis.com/us-en/sites/novartis_us/files/kisqali.pdf. Last accessed: June 16, 2026.
4. FDA. Abemaciclib Prescribing information. 2025. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208716s006s007s008lbl.pdf. Last accessed: June 16, 2026.
5. Hortobagyi GN et al. Updated results from MONALEESA-2, a Phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018;29(7):1541-7.
6. Brett JO et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):85.
7. Toy W et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45(12):1439-45.
8. Gennari A et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021;32(12):1475-95.
9. Patel R et al. An emerging generation of endocrine therapies in breast cancer: a clinical perspective. NPJ Breast Cancer. 2023;9(1):20.
10. Rasha F et al. Mechanisms of endocrine therapy resistance in breast cancer. Mol Cell Endocrinol. 2021;532:111322.
11. Rani A et al. Endocrine resistance in hormone receptor positive breast cancer-from mechanism to therapy. Front Endocrinol (Lausanne). 2019;10:245.
12. Xu XQ et al. Intrinsic and acquired resistance to CDK4/6 inhibitors and potential overcoming strategies. Acta Pharmacol Sin. 2021;42(2):171-8.
13. Stemline Therapeutics, Inc. Elacestrant Prescribing information. 2023. Available at: https://rxmenarinistemline.com/ORSERDU_elacestrant_Full_Prescribing_Information.pdf. Last accessed: June 16, 2026.

MED-05438 / © 2026 Stemline Therapeutics, Inc. All rights reserved. 07/2026