Active Ingredient: Trastuzumab deruxtecan
Trastuzumab deruxtecan as monotherapy is indicated for the treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 6.4 milligrams trastuzumab deruxtecan per kilogram of body weight, once every 3 weeks.
Patients treated with trastuzumab deruxtecan for gastric or gastroesophageal junction cancer should have documented HER2-positive tumour status, defined as a score of 3+ by immunohistochemistry (IHC) or a ratio of ≥2 by in situ hybridization (ISH) or by fluorescence in situ hybridization (FISH), assessed by a CE-marked in vitro diagnostic (IVD) medical device. If a CE-marked IVD is not available, the HER2 status should be assessed by an alternate validated test.
The recommended dose is 6.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
The initial dose should be administered as a 90-minute intravenous infusion. If the prior infusion was well tolerated, subsequent doses of trastuzumab deruxtecan may be administered as 30-minute infusions.
The infusion rate of trastuzumab deruxtecan should be slowed or interrupted if the patient develops infusion-related symptoms. Trastuzumab deruxtecan should be permanently discontinued in case of severe infusion reactions.
No dose adjustment of trastuzumab deruxtecan is required in patients aged 65 years or older. Limited data are available in patients ≥75 years of age.
Trastuzumab deruxtecan is emetogenic, which includes delayed nausea and/or vomiting. Prior to each dose of trastuzumab deruxtecan, patients should be premedicated with a combination regimen of two or three medicinal products (e.g., dexamethasone with either a 5-HT3 receptor antagonist and/or an NK1 receptor antagonist, as well as other medicinal products as indicated) for prevention of chemotherapy- induced nausea and vomiting.
Management of adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of trastuzumab deruxtecan per guidelines provided in Tables 1 and 2.
Trastuzumab deruxtecan dose should not be re-escalated after a dose reduction is made.
Table 1. Dose reduction schedule:
| Dose reduction schedule | Gastric cancer |
|---|---|
| Recommended starting dose | 6.4 mg/kg |
| First dose reduction | 5.4 mg/kg |
| Second dose reduction | 4.4 mg/kg |
| Requirement for further dose reduction | Discontinue treatment |
Table 2. Dose modifications for adverse reactions:
| Adverse reaction | Severity | Treatment modification | |
|---|---|---|---|
| Interstitial lung disease (ILD)/pneumonitis | Asymptomatic ILD/pneumonitis (Grade 1) | Interrupt trastuzumab deruxtecan 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 trastuzumab deruxtecan. • Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected. | ||
| Neutropenia | Grade 3 (less than 1.0-0.5 × 109/L) | • Interrupt trastuzumab deruxtecan until resolved to Grade 2 or less, then maintain dose. | |
| Grade 4 (less than 0.5 × 109/L) | • Interrupt trastuzumab deruxtecan until resolved to Grade 2 or less. • Reduce dose by one level (see Table 1) | ||
| Febrile neutropenia | Absolute neutrophil count of less than 1.0 × 109/L and temperature greater than 38.3°C or a sustained temperature of 38°C or greater for more than one hour. | • Interrupt trastuzumab deruxtecan until resolved. • Reduce dose by one level (see Table 1). | |
| Left ventricular ejection fraction (LVEF) decreased | LVEF greater than 45% and absolute decrease from baseline is 10% to 20% | • Continue treatment with trastuzumab deruxtecan. | |
| LVEF 40% to 45% | And absolute decrease from baseline is less than 10% | • Continue treatment with trastuzumab deruxtecan. • Repeat LVEF assessment within 3 weeks. | |
| And absolute decrease from baseline is 10% to 20% | • Interrupt trastuzumab deruxtecan. • Repeat LVEF assessment within 3 weeks. • If LVEF has not recovered to within 10% from baseline, permanently discontinue trastuzumab deruxtecan. • If LVEF recovers to within 10% from baseline, resume treatment with trastuzumab deruxtecan at the same dose. | ||
| LVEF less than 40% or absolute decrease from baseline is greater than 20% | • Interrupt trastuzumab deruxtecan. • Repeat LVEF assessment within 3 weeks. • If LVEF of less than 40% or absolute decrease from baseline of greater than 20% is confirmed, permanently discontinue trastuzumab deruxtecan. | ||
| Symptomatic congestive heart failure (CHF) | • Permanently discontinue trastuzumab deruxtecan. | ||
Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0).
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. The infusion should be administered at the dose and rate the patient tolerated in the most recent infusion.
Trastuzumab deruxtecan must not be administered as an intravenous push or bolus.
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