Class:
- HER2-directed antibody-drug conjugate (ADC)
Composition:
- Combines the HER2-targeted monoclonal antibody trastuzumab linked to a topoisomerase I inhibitor payload called deruxtecan via a cleavable linker.
Mechanism of Action:
- Trastuzumab binds HER2-expressing cancer cells, facilitating internalization of the ADC.
- Inside the cell, deruxtecan is released, inhibiting topoisomerase I, causing DNA damage and apoptosis.
- The membrane-permeable payload also exerts a bystander killing effect on neighboring tumor cells regardless of HER2 expression level.
Indications:
- HER2-positive metastatic breast cancer previously treated with trastuzumab and other HER2 therapies.
- Also approved for certain HER2-low expressing breast cancers and other HER2-expressing solid tumors in clinical use or trials.
Administration:
- Intravenous infusion every 3 weeks.
Key Toxicities:
- Interstitial lung disease (ILD)/pneumonitis (potentially severe; requires early detection and management)
- Nausea, vomiting
- Neutropenia, anemia, thrombocytopenia
- Fatigue, alopecia
- Elevated liver enzymes
Pharmacist Considerations:
- Monitor closely for respiratory symptoms and promptly evaluate for ILD/pneumonitis.
- Monitor CBC and liver function tests regularly.
- Provide supportive care for GI toxicities and hematologic adverse effects.
- Educate patients about signs of lung toxicity and adherence to follow-up visits.
- Review concomitant medications for interactions; metabolism mainly via CYP3A4.
Synonyms
Fam-trastuzumab deruxtecan, Enhertu