HER2-positive breast cancer

Active Ingredient: Trastuzumab deruxtecan

Indication for Trastuzumab deruxtecan

Population group: only adults (18 years old or older)
Therapeutic intent: Curative procedure

Trastuzumab deruxtecan as monotherapy 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.

For this indication, competent medicine agencies globally authorize below treatments:

5.4 mg/kg once every 3 weeks

For:

Dosage regimens

Intravenous, 5.4 milligrams trastuzumab deruxtecan per kilogram of body weight, once every 3 weeks.

Detailed description

The recommended dose of trastuzumab deruxtecan is 5.4 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. Antiemetics may be administered in accordance with local medical practice as per patient tolerance for prophylaxis or management.

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.

Trastuzumab deruxtecan should not be substituted with trastuzumab or trastuzumab emtansine.

Delayed or missed dose

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.

Dose modifications

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
(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 reactionSeverity Treatment modification
Interstitial lung
disease
(ΔΠΠ)/(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 (see section 4.4).
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
Febrile neutropeniaAbsolute 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 4.03 (NCI-CTCAE v.4.03).

Dosage considerations

Trastuzumab deruxtecan must not be administered as an intravenous push or bolus.

Active ingredient

Trastuzumab deruxtecan

Trastuzumab deruxtecan is a HER2-targeted antibody-drug conjugate. The antibody is a humanised anti-HER2 IgG1 attached to deruxtecan, a topoisomerase I inhibitor (DXd) bound by a tetrapeptide-based cleavable linker.

Read more about Trastuzumab deruxtecan

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