Source: FDA, National Drug Code (US) Revision Year: 2020
ENHERTU is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.
This indication is approved under accelerated approval based on tumor response rate and duration of response [see Clinical Studies (14.1)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Do not substitute ENHERTU for or with trastuzumab or ado-trastuzumab emtansine.
The recommended dosage of ENHERTU is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
First infusion: Administer infusion over 90 minutes.
Subsequent infusions: Administer over 30 minutes if prior infusions were well tolerated.
Slow or interrupt the infusion rate if the patient develops infusion-related symptoms.
Permanently discontinue ENHERTU in case of severe infusion reactions.
Management of adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of ENHERTU as described in Tables 1 and 2.
Do not re-escalate the ENHERTU dose after a dose reduction is made.
If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle. Adjust the schedule of administration to maintain a 3-week interval between doses. Administer the infusion at the dose and rate the patient tolerated in the most recent infusion.
Table 1. Dose Reduction Schedule:
| Dose Reduction Schedule (Starting dose is 5.4 mg/kg.) | Dose to be administered |
|---|---|
| First dose reduction | 4.4 mg/kg |
| Second dose reduction | 3.2 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 ENHERTU 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 [see Warnings and Precautions (5.1)]. | |
| Symptomatic ILD/pneumonitis (Grade 2 or greater) | • Permanently discontinue ENHERTU. • Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected [see Warnings and Precautions (5.1)]. | ||
| Neutropenia | Grade 3 (less than 1.0 to 0.5 × 109/L) | • Interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. | |
| Grade 4 (less than 0.5 × 109/L) | • Interrupt ENHERTU 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 ENHERTU until resolved. • Reduce dose by one level (see Table 1). | |
| Left Ventricular Dysfunction | LVEF greater than 45% and absolute decrease from baseline is 10% to 20% | • Continue treatment with ENHERTU. | |
| LVEF 40% to 45% | And absolute decrease from baseline is less than 10% | • Continue treatment with ENHERTU. • Repeat LVEF assessment within 3 weeks. | |
| And absolute decrease from baseline is 10% to 20% | • Interrupt ENHERTU. • Repeat LVEF assessment within 3 weeks. • If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. • If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. | ||
| LVEF less than 40% or absolute decrease from baseline is greater than 20% | • Interrupt ENHERTU. • 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 ENHERTU. | ||
| Symptomatic congestive heart failure (CHF) | • Permanently discontinue ENHERTU. | ||
| Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v.4.03). | |||
In order to prevent medication errors, check the vial labels to ensure that the drug being prepared and administered is ENHERTU (fam-trastuzumab deruxtecan-nxki) and not trastuzumab or ado-trastuzumab emtansine.
Reconstitute and further dilute ENHERTU prior to intravenous infusion. Use appropriate aseptic technique.
ENHERTU (fam-trastuzumab deruxtecan-nxki) is a cytotoxic drug. Follow applicable special handling and disposal procedures.1
Reconstitution:
Dilution:
Administration:
Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of reconstitution. Do not freeze. Do not shake the reconstituted or diluted solution [see Dosage and Administration (2.3)].
ENHERTU (fam-trastuzumab deruxtecan-nxki) is a cytotoxic drug. Follow applicable special handling and disposal procedures.1
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