Active Ingredient: Datopotamab deruxtecan
Datopotamab deruxtecan as monotherapy is indicated for the first-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 6 milligrams datopotamab deruxtecan per kilogram of body weight, once every 3 weeks.
The recommended dose of datopotamab deruxtecan is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) of body weight given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
Prior to each infusion of datopotamab deruxtecan, a premedication regimen for the prevention of infusion-related reactions that consists of an antihistamine and paracetamol (with or without glucocorticoids) should be considered.
It is also recommended that patients receive prophylactic antiemetic agents (dexamethasone with 5-HT3 antagonists as well as other medicinal products, such as NK1 receptor antagonists) prior to infusion of datopotamab deruxtecan and on subsequent days as needed.
The infusion rate of datopotamab deruxtecan should be slowed or interrupted if the patient develops an infusion-related reaction. Datopotamab deruxtecan should be permanently discontinued in case of life-threatening infusion-related reactions.
Management of adverse reactions may require dose delay, dose reduction, or treatment discontinuation per guidelines provided in Tables 1 and 2.
Datopotamab deruxtecan dose should not be re-escalated after a dose reduction is made.
Table 1. Dose reductions for adverse reactions:
| Recommended starting dose | 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) |
| First dose reduction | 4 mg/kg (up to a maximum of 360 mg for patients ≥90 kg) |
| Second dose reduction | 3 mg/kg (up to a maximum of 270 mg for patients ≥90 kg) |
| Third dose reduction | Permanently discontinue |
Table 2. Dose modifications for adverse reactions:
| Adverse reaction | Severity* | Dose modification |
|---|---|---|
| Interstitial lung disease (ILD)/pneumonitis | Asymptomatic ILD/pneumonitis (Grade 1) | Delay dose until resolved to Grade 0#, then: • if resolved in 28 days or less from date of onset, maintain dose. • if resolved in greater than 28 days from date of onset, reduce dose one level (see Table 1). • consider corticosteroid treatment as soon as ILD/pneumonitis is suspected. |
| Symptomatic ILD/pneumonitis (Grade 2 or greater) | • Permanently discontinue. • Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected. | |
| Keratitis | Grade 2 | • Delay dose until resolved to Grade 1 or less, then maintain dose. |
| Grade 3 | • Delay dose until resolved to Grade 1 or less, then reduce the dose by 1 level (see Table 1). | |
| Grade 4 | • Permanently discontinue. | |
| Stomatitis | Grade 2 | • Delay dose until resolved to Grade 1 or less. • Restart at the same dose for first occurrence. • Consider restarting at reduced dose level (see Table 1) if recurrent. |
| Grade 3 | • Delay dose until resolved to Grade 1 or less. • Restart at reduced dose level (see Table 1). | |
| Grade 4 | • Permanently discontinue. |
* Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
# Grade 0 refers to full resolution of ILD/pneumonitis, including the disappearance of radiological findings associated with active ILD/pneumonitis. Residual scarring or fibrosis following recovery of ILD/pneumonitis is not considered to be active disease.
If a planned dose is delayed or missed, it should be administered as soon as possible without waiting until the next planned cycle. The schedule of administration should be adjusted to maintain a 3-week interval between doses.
No dose adjustment of datopotamab deruxtecan is required in patients aged 65 years or older. Data from datopotamab deruxtecan in patients aged 85 years or older are limited.
Datopotamab deruxtecan must not be administered as an intravenous push or bolus.
The first infusion is to be administered over 90 minutes. Patients should be observed during the infusion and for at least 30 minutes following the initial dose for signs or symptoms of infusion-related reactions.
Subsequent infusions are to be administered over 30 minutes if prior infusions were tolerated. Patients should be observed during the infusion and for at least 30 minutes after infusion.
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