EGFR Inhibitors (Epidermal Growth Factor Receptor Inhibitors)
Class / Mechanism
- EGFR inhibitors block the EGFR (ErbB1/HER1) signaling pathway, which is involved in cell proliferation, survival, angiogenesis, and metastasis.
- Two main classes:
- Monoclonal antibodies (mAbs) – bind extracellular domain of EGFR.
- Tyrosine kinase inhibitors (TKIs) – block intracellular tyrosine kinase domain.
Common EGFR Inhibitors
| Drug (Brand) | Class | Primary Indications | Administration | Key Toxicities / Monitoring |
|---|---|---|---|---|
| Cetuximab (Erbitux) | mAb | KRAS wild-type metastatic colorectal cancer, head & neck SCC | IV weekly or biweekly | Infusion reactions, acneiform rash, hypomagnesemia, diarrhea; monitor Mg, electrolytes |
| Panitumumab (Vectibix) | mAb | KRAS wild-type metastatic colorectal cancer | IV every 2 weeks | Similar to cetuximab; rash, hypomagnesemia, diarrhea; monitor electrolytes |
| Necitumumab (Portrazza) | mAb | Squamous NSCLC (1L, with chemo) | IV every 2 weeks | Infusion reactions, thromboembolism, rash, hypomagnesemia |
| Erlotinib (Tarceva) | TKI | EGFR-mutant NSCLC, pancreatic cancer (with gemcitabine) | Oral daily | Rash, diarrhea, interstitial lung disease (ILD), hepatotoxicity; monitor LFTs, pulmonary status |
| Gefitinib (Iressa) | TKI | EGFR-mutant NSCLC | Oral daily | Rash, diarrhea, ILD; monitor LFTs, pulmonary status |
| Afatinib (Gilotrif) | TKI (irreversible) | EGFR-mutant NSCLC | Oral daily | Diarrhea, rash, stomatitis, ILD; monitor LFTs, pulmonary status |
| Osimertinib (Tagrisso) | TKI (3rd generation, EGFR T790M) | EGFR T790M+ NSCLC, first-line EGFR-mutant NSCLC | Oral daily | Diarrhea, rash, QT prolongation, ILD; monitor ECG, LFTs, pulmonary status |
Class Toxicities
- Skin toxicity (acneiform rash) → may correlate with efficacy.
- Diarrhea → manage aggressively to prevent dehydration.
- Hypomagnesemia / electrolyte disturbances (mAbs) → monitor Mg, Ca, K.
- Interstitial lung disease / pneumonitis (TKIs) → rare but serious; monitor for dyspnea, cough.
- Hepatotoxicity → monitor LFTs, especially with TKIs.
- Infusion reactions (mAbs) → premedicate with antihistamines and monitor during first infusion.
Pharmacist Pearls
- Test for EGFR mutation status before initiating TKI therapy in NSCLC.
- KRAS wild-type status required for anti-EGFR monoclonal antibodies in colorectal cancer.
- Drug interactions: TKIs metabolized via CYP3A4 (watch inhibitors/inducers).
- Patient counseling: skin care, diarrhea management, and monitoring for pulmonary symptoms.
- Oral TKIs: emphasize adherence and consistent administration.
Summary:
- EGFR inhibitors = mAbs (extracellular blockade) or TKIs (intracellular blockade).
- Key toxicities: rash, diarrhea, electrolyte disturbances, hepatotoxicity, ILD.
- Molecular testing (EGFR mutation, KRAS wild-type) is essential before therapy.