ORSERDU Elacestrant tablets

I. Basic Drug Information

Generic Name: Elacestrant

Brand Name: ORSERDU

Dosage Form & Strength: 345 mg/tablet; 30 tablets/box

Manufacturer: Lao United Pharmaceutical Group Co., Ltd.

Approval Number (Lao National Drug Administration): 11 L 1258/24

Storage Conditions: 20°C–25°C (excursions permitted between 15°C–30°C); protect from light and moisture.

II. Indications

Indicated for the treatment of patients with advanced or metastatic breast cancer that is estrogen receptor (ER)-positive, HER2-negative, and *ESR1*-mutated, provided that the following criteria are met:

Postmenopausal women or adult men;

Disease progression has occurred following at least one prior line of endocrine therapy.

Note: *ESR1* mutation status must be confirmed via genomic testing prior to initiating treatment.

III. Mechanism of Action

Elacestrant is an oral selective estrogen receptor degrader (SERD):

It binds to estrogen receptor-alpha (ERα), inducing conformational changes that lead to the degradation of the ER protein via the proteasomal pathway;

It blocks estrogen-dependent signaling pathways, thereby inhibiting tumor cell proliferation;

It has demonstrated antitumor activity in models resistant to fulvestrant or CDK4/6 inhibitors, as well as in models harboring *ESR1* mutations.

IV. Dosage and Administration

1. Standard Dosing Regimen

Dosage: 345 mg (1 tablet) once daily;

Administration: Swallow the tablet whole with food (do not chew, crush, or split); take at approximately the same time each day;

Duration of Treatment: Continue treatment until disease progression or until intolerable toxicity occurs. 2. Dosage Adjustment

Missed Doses or Vomiting:

Missed dose > 6 hours or vomiting after administration → Skip the missed dose; resume normal dosing the following day. Do not take a double dose to make up for the missed one.

Hepatic Impairment:

| Hepatic Impairment Classification | Dosage Adjustment

| Moderate Impairment (Child-Pugh B) | Reduce dose to 258 mg/day

| Severe Impairment (Child-Pugh C) | Contraindicated

Dosage Adjustment for Adverse Reactions:

Table 1: Dosage Adjustment Guidelines Based on Adverse Reaction Severity

| Adverse Reaction Grade | Management Measures

| Grade 1 | Continue current dose

| Grade 2 | Suspend treatment until recovery to ≤ Grade 1 → Resume at original dose

| Grade 3 | Suspend treatment until recovery to ≤ Grade 1 → Reduce dose by one level (1st reduction: 258 mg; 2nd reduction: 172 mg)

| Grade 4 | Suspend treatment until recovery to ≤ Grade 1 → Permanently discontinue treatment OR reduce dose by one level (permanently discontinue if reaction recurs)

3. Drug Interactions

Concomitant Use Contraindicated: Strong/moderate CYP3A4 inducers (e.g., rifampin) or inhibitors (e.g., ketoconazole).

Antacids/Dairy Products: Calcium- or magnesium-containing products may reduce absorption; administer at a separate time interval.

V. Adverse Reactions

Common Adverse Reactions (Incidence > 10%)

Musculoskeletal: Pain (highest incidence);

Gastrointestinal: Nausea, vomiting, diarrhea, constipation, abdominal pain;

Laboratory Abnormalities:

Elevated cholesterol (30%), elevated triglycerides (27%);

Elevated AST/ALT, hyponatremia, elevated creatinine;

Systemic Symptoms: Fatigue, hot flashes, headache.

Serious Risk Warnings

Dyslipidemia:

Grade 3/4 hypercholesterolemia (0.9%) and hypertriglyceridemia (2.2%); lipid levels require periodic monitoring.

Embryo-Fetal Toxicity: Animal studies have demonstrated teratogenicity; contraindicated in pregnant women.

Other: Rare, but vigilance is required regarding hepatic function abnormalities and thrombotic risk. VI. Contraindications and Precautions

1. Pregnancy and Lactation:

Absolutely contraindicated in pregnant women (risk of fetal malformation);

Patients of childbearing potential (including men) must employ effective contraception during treatment and for one week following the last dose;

During lactation, discontinue the medication and suspend breastfeeding until one week after the last dose.

2. Lipid Monitoring:

Monitor blood lipid levels prior to treatment and every three months during treatment; intervene if abnormalities are detected.

3. Special Populations:

Hepatic Impairment: Dosage reduction is required for patients with moderate impairment; contraindicated in patients with severe impairment;

Elderly Patients: No difference in safety profile observed in patients >65 years of age; data are limited for patients >75 years of age.

VII. Key Clinical Efficacy Data

Progression-Free Survival (PFS): In patients with *ESR1* mutations, PFS was extended by several months compared to conventional regimens (EMERALD trial);

Tumor Response: Tumor lesions shrank in a subset of patients, demonstrating particular efficacy in those with prior resistance to endocrine therapy.

Note: Specific medication use should be guided by genetic testing and clinical assessment; strictly adhere to physician's instructions and regularly monitor blood lipids, liver function, and platelet counts.