Datopotamab deruxtecan (Datroway) is a Trop-2-targeted antibody-drug conjugate (ADC) indicated for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

How to Use Datopotamab deruxtecan (Datroway)

Administration Route and Frequency

Datopotamab deruxtecan is for intravenous infusion only; intravenous push or rapid injection is prohibited.

The recommended dose is 6mg/kg (maximum dose of 540mg for patients with body weight ≥90kg), administered intravenously once every 3 weeks (21 days as one cycle) until disease progression or unacceptable toxicity occurs.

If a scheduled dose is delayed or missed, administer the missed dose as soon as possible; do not wait until the next scheduled cycle.

Premedication and Concomitant Medications

Preservative-free lubricating eye drops (at least 4 times daily).

Steroid-containing mouthwash (dexamethasone oral solution 0.1mg/mL, 4 times daily).

Antihistamine (diphenhydramine 25-50mg, intravenous or oral).

Antipyretic (paracetamol 650-1000mg, intravenous or oral).

Antiemetic (5-HT3 receptor antagonist or appropriate alternative).

Preparation Method

Reconstitution: Slowly inject 5mL of sterile water for injection into each 100mg vial, and gently swirl until completely dissolved (do not shake); the final concentration is 20mg/mL.

The reconstituted solution should be clear, colorless to pale yellow; do not use if particles or discoloration are observed.

Dilution: Dilute with 100mL of 5% dextrose injection; normal saline (sodium chloride injection) is prohibited.

The infusion bag material should be polyvinyl chloride (PVC) or polyolefin.

Administration Method

First infusion: Complete within 90 minutes; observe for at least 1 hour after infusion.

Second infusion: If the first infusion is well tolerated, complete within 30 minutes; observe for at least 1 hour after infusion.

Subsequent infusions: If previous infusions are well tolerated, complete within 30 minutes; observe for at least 30 minutes after infusion.

Dosage Adjustment of Datopotamab deruxtecan (Datroway)

Principles of Dosage Adjustment

Dosage adjustment of Datopotamab deruxtecan is based on the severity of adverse reactions.

Dosage adjustment should not be too frequent; the peak therapeutic effect may take 4-6 weeks to appear.

First dose reduction: 4mg/kg (maximum 360mg).

Second dose reduction: 3mg/kg (maximum 270mg).

Third dose reduction: Permanent discontinuation of the drug.

Ocular Adverse Reactions

Non-confluent superficial keratitis: Suspend administration until improvement or resolution.

Confluent superficial keratitis or visual acuity decrease ≥3 lines: Suspend administration until improvement or resolution, then reduce the dose by one level.

Corneal ulcer or stromal opacity: Permanently discontinue the drug.

Stomatitis/Oral Mucositis

Grade 1: Optimize preventive and supportive medications.

Grade 2: Suspend administration until resolution to.

Grade 3: Suspend administration until resolution to ≤Grade 1, then reduce the dose by one level.

Grade 4: Permanently discontinue the drug.

Medication for Special Populations of Datopotamab deruxtecan (Datroway)

Patients with Renal Impairment

Patients with mild to moderate renal impairment (CLcr 30-<90 mL/min) may have an increased incidence of ILD/pneumonitis; close monitoring of respiratory responses is required.

No dosage adjustment is needed for patients with mild to moderate renal impairment.

The pharmacokinetic impact in patients with severe renal impairment (CLcr <30 mL/min) is not yet clear.

Patients with Hepatic Impairment

No dosage adjustment is needed for patients with mild hepatic impairment (total bilirubin ≤ULN with any AST >ULN, or total bilirubin >1-1.5×ULN with any AST).

Patients with moderate hepatic impairment (total bilirubin >1.5-3×ULN with any AST) should be closely monitored for adverse reactions.

The recommended dose for severe hepatic impairment (total bilirubin >3×ULN with any AST) has not been established.

Pregnancy

Datopotamab deruxtecan may cause fetal harm, as its topoisomerase inhibitor component (DXd) is genotoxic.

Women of childbearing age should confirm their pregnancy status before treatment.

Effective contraceptive measures should be used during treatment and for 7 months after the last dose.

Lactation

There are no data on whether Datopotamab deruxtecan is excreted into human milk.

It is recommended to discontinue breastfeeding during treatment and for 1 month after the last dose.