Lapatinib

Drug Class

• Oral multi-targeted tyrosine kinase inhibitor (TKI)
• Specifically targets HER2 (ErbB2) and EGFR (ErbB1) receptors

Mechanism of Action

• Inhibits intracellular tyrosine kinase domains of:
  • HER2 (human epidermal growth factor receptor 2)
  • EGFR (epidermal growth factor receptor)
• Blocks downstream signaling pathways involved in cell proliferation and survival (e.g., MAPK and PI3K/AKT pathways)
• Especially effective in tumors that overexpress HER2

Main Clinical Indications

• HER2-positive metastatic breast cancer, especially in:
  • Patients who have progressed on trastuzumab therapy
  • Often used in combination with capecitabine
• Investigational/less common: HER2-overexpressing tumors in other sites (e.g., gastric or biliary cancers)

Note: Lapatinib is not used for renal cell carcinoma or GIST — those are treated with drugs like sunitinib or pazopanib

Common Adverse Effects

• Diarrhea (most common)
• Rash (acneiform, EGFR-related)
• Hepatotoxicity (↑ AST/ALT, rare liver failure)
• Hand-foot syndrome (especially when combined with capecitabine)
• Decreased left ventricular ejection fraction (LVEF) – less common but serious
• Fatigue, nausea, loss of appetite

Clinical Considerations

• Given orally, usually once daily
• Metabolized by CYP3A4 → watch for drug interactions
• Monitor:
  • Liver function tests (LFTs)
  • Ejection fraction (baseline and during treatment)
• May cross the blood-brain barrier, potentially useful in brain metastases
• Resistance can develop through mutations or activation of alternative pathways