Cycle length: 3 weeks.
Duration of therapy: Until disease progression or unacceptable toxicity. |
| Drug | Dose and route | Administration | Given on days |
| Trastuzumab deruxtecan¶ | 5.4 mg/kg IV | Dilute in 100 mL D5WΔ and administer first infusion over 90 minutes◊ and subsequent infusions over 30 minutes,◊ if first infusion was tolerated. | Day 1 |
| Pretreatment considerations: |
| Emesis risk | - MODERATE (30 to 90% risk of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - No standard premedication regimen.
- Refer to UpToDate topics on infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy.
|
| Infection prophylaxis | - Primary prophylaxis with G-CSF is not indicated. Grade 3 or greater neutropenia was 13.7% in this trial; however, the incidence of febrile neutropenia was low.[1]
- Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
|
| Cardiopulmonary issues | - Trastuzumab deruxtecan is associated with cardiotoxicity; assess baseline LVEF prior to therapy. Patients with baseline LVEF <50% were excluded from this study.[1]
- Trastuzumab deruxtecan may cause severe, life-threatening pulmonary toxicity and should be used with caution in patients with preexisting pulmonary disease. Higher incidence of grade 1 and 2 ILD/pneumonitis in patients with moderate kidney impairment.[2]
- Refer to UpToDate topics on cardiotoxicity of trastuzumab and other HER2-targeted agents, and pulmonary toxicity associated with antineoplastic therapy, molecularly targeted agents.
|
| Embryo-fetal toxicity | - Trastuzumab deruxtecan may cause embryo-fetal harm.[2] Advise patients of these risks and discuss effective contraception.
|
| Monitoring parameters: |
- Obtain CBC with differential and platelet count prior to each treatment cycle.
|
- Monitor for infusion reactions.
|
- Assess cardiac function at baseline and then as clinically indicated. In the clinical trial, LVEF was measured at baseline and then every 4 cycles.[1]
|
- Monitor for cough, dyspnea, fever, or any worsening respiratory symptoms.
|
- Evaluate pregnancy status (obtain pregnancy test prior to therapy).
|
| Suggested dose modifications for toxicity:§ |
| Myelotoxicity | - For grade 3 neutropenia, hold until resolves to grade 2 or less and maintain same dose level. For grade 4 neutropenia, reduce 1 dose level when resolves to grade 2 or less.
- For grade 3 thrombocytopenia, hold until resolves to grade 1 or less and maintain same dose level. Reduce 1 dose level when resolves to grade 1 or less for grade 4 thrombocytopenia.
- For febrile neutropenia, reduce 1 dose level when resolved.
|
| Cardiotoxicity | - If LVEF is greater than 45% and absolute decrease from baseline is 10 to 20%, continue treatment with trastuzumab deruxtecan.
- If the LVEF drops to 40 to 45%:
- And absolute decrease from baseline is <10%, continue trastuzumab deruxtecan treatment and repeat LVEF assessment within 3 weeks.[1,2]
- And absolute decrease from baseline is 10 to 20%, interrupt trastuzumab deruxtecan and 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 trastuzumab deruxtecan at the same dose.[1,2]
- If LVEF drops to <40% or absolute decrease from baseline of greater than 20%, then interrupt treatment. Repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue trastuzumab deruxtecan.
- If symptomatic heart failure, permanently discontinue trastuzumab deruxtecan. Guidelines for managing cardiac dysfunction during therapy with HER2-targeted agents are available.[1,2]
- Refer to UpToDate topics on cardiotoxicity of trastuzumab and other HER2-targeted agents.
|
| Pulmonary toxicity | - For asymptomatic ILD/pneumonitis (grade 1 or less), consider corticosteroids and hold until resolves to grade 0. If resolves in 28 days or less, then maintain same dose level. If resolves after 28 days, then reduce one dose level.[1,2]
- For symptomatic ILD/pneumonitis (grade 2 or greater), initiate corticosteroids and permanently discontinue trastuzumab deruxtecan.
|
| Infusion reaction | - Slow or interrupt the infusion rate if the patient develops infusion-related symptoms.[1]
- For severe infusion reactions, permanently discontinue.
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
