II. Indications
-
Colorectal Cancer (metastatic, wild-type K-RAS, EGFR positive)
- Cetuximab
- Panitumumab
- Squamous cell cancer of the head and neck
- Cetuximab
-
Non-Small Cell Lung Cancer (metastatic, squamous cell)
- Necitumumab
- Cetuximab (off-label)
-
Squamous Cell Skin Cancer (non-resectable)
- Cetuximab (off-label)
III. Mechanism
-
Epidermal Growth Factor Receptor (EGFR, HER1)
- EGFR is Tyrosine Kinase that is activated by specific Ligands on cells of epidermal-lineage
- Binding triggers cascade that leads to epithelial cell growth, development and homeostasis
- May also trigger cancer cell proliferation, invasion and migration
- EGFR Tyrosine Kinase mutations and amplifications
- Seen in a variety of cancers (e.g. lung, Breast, brain)
- EGFR Monoclonal Antibody
- Recombinant, chimeric Monoclonal Antibody targeting Epidermal Growth Factor Receptor (EGFR, HER1)
- Binds extracellular EGFR on the cell surface preventing receptor binding and activation
- Cetuximab (Erbitux): Used in Colon Cancer and head and neck tumors
- Panitumumab (Vectibix): Used in Colon Cancer
- EGFR agents have been effective in metastatic Colorectal Cancer (without RAS mutation)
- Other agents targeting EGFR
IV. Medications
- Cetuximab (Erbitux) IV Solution
- Risk of Anaphylaxis, Cardiac Arrest, infusion reaction, lung toxicity, Pulmonary Embolism, Renal Failure, Sepsis
- Also risk of skin rash including exfoliation (95% of patients, severe in 16%)
- Necitumumab (Portrazza) IV Solution
- Risk of Cardiac Arrest, infusion reaction, arterial thrombosis, Pulmonary Embolism, severe dermatitis
- Panitumumab (Vectibix) IV Solution
- Risk of Anaphylaxis, infusion reaction, ocular toxicity, lung toxicity, dermatitis (90% of patients, 15% severe)
V. Dosing
- See other references for disease specific dosing protocols
VI. Adverse Effects
- Cardiopulmonary
- Cardiac Arrest (FDA black box, Cetuximab, Necitumumab)
- Serious infusion reaction including fatal reactions (Cetuximab, Necitumumab, Panitumumab)
- Lung toxicity including intersititial lung disease or pulmonary fibrosis (Cetuximab, Panitumumab)
- Pulmonary Embolism (Cetuximab, Necitumumab)
- Arterial Thrombosis (Necitumumab)
- Dermatologic
- Skin rash including exfoliation (Cetuximab, , Necitumumab, Panitumumab )
- Dermatitis often is an indicator that the EGFR Inhibitor is working
- Acne
- Gastrointestinal
- Diarrhea occurs in 50% of patients on EGFR Inhibitors
- Renal
- Acute Kidney Injury (Cetuximab)
- Hypomagnesemia (Cetuximab, Necitumumab)
- Eye
VII. Safety
- Avoid in Lactation
- Avoid in pregnancy (all trimesters, Pregnancy category X)
- Use reliable Contraception
- Monitoring
- Serum Electrolytes (during treatment and for 8 weeks after)
VIII. Resources
- Cetuximab (DailyMed)
- Panitumumab (DailyMed)
- Necitumumab (DailyMed)