- Drug Class: Antibody–Drug Conjugate (ADC).
- Components:
- Antibody: A humanized IgG1κ monoclonal antibody directed against Trop-2 (trophoblast cell-surface antigen 2), which is overexpressed in many epithelial cancers.
- Cytotoxic payload: SN-38, the active metabolite of irinotecan, a topoisomerase I inhibitor.
- Linker: Hydrolyzable linker that allows controlled release of SN-38 inside and around tumor cells.
Mechanism of Action (MOA):
- Antibody binds to Trop-2 on tumor cells.
- Complex undergoes internalization → linker cleavage releases SN-38.
- SN-38 inhibits topoisomerase I, preventing DNA religation, leading to DNA breaks, cell cycle arrest, and apoptosis.
- Payload can also diffuse locally (“bystander effect”) to kill adjacent tumor cells.
Indications (FDA-approved):
- Triple-negative breast cancer (TNBC): Adults with unresectable locally advanced or metastatic TNBC after ≥2 prior therapies.
- Hormone receptor–positive, HER2-negative breast cancer: After endocrine therapy and ≥2 systemic therapies.
- Metastatic urothelial carcinoma: After platinum-based chemotherapy and PD-1/PD-L1 inhibitor.
Key Toxicities / Adverse Effects:
- Myelosuppression (especially neutropenia, anemia, thrombocytopenia).
- Severe diarrhea (due to SN-38, like irinotecan).
- Nausea/vomiting, fatigue, alopecia, decreased appetite.
- Hypersensitivity reactions (due to antibody component).
- Rare but serious: febrile neutropenia, sepsis, intestinal obstruction, pneumonitis.
Dosing (Adult):
- 10 mg/kg IV on Days 1 and 8 of a 21-day cycle, until disease progression or unacceptable toxicity.
- Premedication recommended: antipyretics, antihistamines, and antiemetics.
Clinical Pharmacist Monitoring Points:
- CBC with differential (before each dose).
- Diarrhea severity and hydration status.
- Signs of infusion reactions.
- Hepatic function (SN-38 metabolism depends on UGT1A1; patients with UGT1A1*28 polymorphism are at ↑ risk of neutropenia and diarrhea).
- Supportive care: G-CSF for neutropenia, antidiarrheal therapy (e.g., loperamide).
In summary:
Sacituzumab govitecan is a Trop-2–directed ADC that delivers SN-38 (a topoisomerase I inhibitor) directly to cancer cells. It is mainly used in advanced breast and urothelial cancers, with major pharmacist concerns being neutropenia, diarrhea, and UGT1A1 metabolism.
Synonyms
Trodelvy