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Trastuzumab Deruxtecan (T-DXd): HER2-Targeted ADC Therapy

Topoisomerase I inhibitor payload delivered via HER2-directed antibody

Written by: Saygı Hospital Health Guide Editorial Board
Last updated:

This content has been compiled by the Saygı Hospital Health Guide Editorial Board and is periodically reviewed by a specialist physician.

References (5)

This content is for informational purposes only and does not constitute medical advice. You can book an appointment at our Onkoloji department. Book Appointment →

What is Trastuzumab Deruxtecan (T-DXd): HER2-Targeted ADC Therapy?

Trastuzumab deruxtecan delivers deruxtecan, a topoisomerase I inhibitor exatecan derivative, to HER2-expressing tumor cells.

The drug-to-antibody ratio of approximately 8 enables potent cytotoxic activity with bystander effect impacting neighboring HER2-low cells.

Approved indications include HER2-positive metastatic breast cancer after prior anti-HER2 therapy, HER2-low metastatic breast cancer, HER2-positive gastric or gastroesophageal junction adenocarcinoma and HER2-mutant non-small cell lung cancer.

HER2 testing by immunohistochemistry, in situ hybridization or next-generation sequencing identifies eligible patients.

Pharmacokinetics support every 3-week intravenous administration with significant tissue penetration.

Symptoms

T-DXd is a treatment, not a disease; therapeutic effects depend on the underlying cancer.
Common adverse effects include nausea, vomiting, fatigue, alopecia, decreased appetite and constipation.
Cytopenias including neutropenia, thrombocytopenia and anemia require monitoring.
Interstitial lung disease and pneumonitis are critical adverse events requiring prompt recognition and management.
Cardiac toxicity with decreased left ventricular ejection fraction is monitored throughout treatment.

Risk Factors

Pre-existing pulmonary disease, lung radiation history or impaired pulmonary function increase ILD risk.
Renal or hepatic impairment may require dose adjustments.
Pregnancy and breastfeeding are contraindications due to embryofetal toxicity.
Concurrent medications affecting CYP3A4 or P-glycoprotein may alter pharmacokinetics.
Cardiac risk factors and prior anthracycline exposure warrant careful monitoring of left ventricular function.

When to See a Doctor?

If you experience any of the following symptoms, seek medical attention promptly:

  • New onset cough, dyspnea, fever or hypoxia requires urgent evaluation for interstitial lung disease.
  • Severe nausea, vomiting, dehydration or inability to maintain oral intake needs medical assessment.
  • Febrile neutropenia, severe bleeding or unusual bruising requires immediate intervention.
  • Symptoms of heart failure including dyspnea, lower extremity edema or fatigue need cardiac evaluation.
  • Vision changes, severe abdominal pain or new neurologic symptoms warrant prompt review.

Treatment Methods

01
Standard dosing in breast cancer is 5.4 mg/kg every 3 weeks; in gastric cancer 6.4 mg/kg every 3 weeks.
02
Premedication with antiemetics is essential; corticosteroids and serotonin antagonists are commonly used.
03
Baseline and serial cardiac function monitoring with echocardiography or MUGA scan is performed.
04
Pulmonary symptoms warrant high-resolution CT, pulmonary function tests and consideration of corticosteroids; treatment must be permanently discontinued for grade 2 or higher pneumonitis in some indications.
05
Dose interruptions, reductions or discontinuation are based on toxicity grade; supportive care including growth factor support, transfusion and infection prophylaxis as needed; ongoing trials evaluate combinations and earlier line use.

Which Department to Visit?

You can visit our Onkoloji department for these complaints. Our specialist physicians will create the most suitable treatment plan for you.

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Health Disclaimer: The information on this page is prepared for general informational purposes only. It does not replace medical diagnosis and treatment. Please consult your physician for your complaints. Saygı Hospital does not accept responsibility for actions taken based on the information on this page.