necitumumab

Action and Spectrum

Necitumumab is a monoclonal antibody that targets EGFR, blocking its activation and downstream signaling, which inhibits cancer cell growth, survival, and angiogenesis. It also enhances immune response through antibody-dependent cellular cytotoxicity (ADCC). It is approved for use in combination with chemotherapy (gemcitabine and cisplatin) for the treatment of metastatic squamous non-small cell lung cancer (NSCLC). Its role is specific to tumors that express EGFR and is not recommended for use in non-squamous NSCLC due to a lack of demonstrated benefit and increased risk of adverse effects. 

Drug Interaction

Adverse Reaction

Adverse drug reactions:   

Frequency defined   

>10%:   

Headache   

Skin toxicity   

Skin rash   

Acneiform eruption   

Hypomagnesemia   

Hypocalcemia   

Hypophosphatemia   

Hypokalemia   

Weight loss   

Vomiting   

Diarrhea   

Stomatitis   

1% to 10%:   

Venous thromboembolism   

Arterial thromboembolism    

Pulmonary embolism   

Cardiorespiratory arrest   

Deep vein thrombosis    

Cerebrovascular accident   

Ischemia   

Myocardial infarction   

Acne vulgaris   

Paronychia   

Pruritus   

Xeroderma   

Skin fissure   

Antibody development    

Conjunctivitis   

Hemoptysis    

Black Box Warning

Necitumumab carries a black box warning for the risk of cardiopulmonary arrest and hypomagnesemia. It can cause fatal or life-threatening cardiac arrest, particularly when used with cisplatin-based chemotherapy in patients with squamous non-small cell lung cancer. 

Contraindication / Caution

Contraindications 

Known hypersensitivity to necitumumab or any of its components. 

Cautions 

Cardiopulmonary Arrest 

Electrolyte Imbalances 

Thromboembolic Events 

Infusion Reactions 

Pregnancy / Lactation

Pregnancy warnings:    

• US FDA pregnancy category: not assigned 

Breastfeeding warnings: 

• The release of the drug into the human breastmilk is unknown  

Pregnancy Categories:      

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first trimester or the later trimester      
• Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women      
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a result in humans must take care of potential risks in pregnant women      
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits      
• Category X: Drugs listed in this category outweigh risks over benefits Hence these categories of drugs need to be avoided by pregnant women      
• Category N: There is no data available for the drug under this category     

Pharmacology

Necitumumab is a fully human IgG1 monoclonal antibody that selectively binds to the epidermal growth factor receptor (EGFR) on the surface of tumor cells. By binding to the extracellular domain of EGFR, it blocks ligand-induced activation of the receptor, thereby inhibiting downstream signaling pathways like RAS-RAF-MEK-ERK and PI3K-AKT, which are responsible for promoting cell proliferation, survival, and angiogenesis. 

Pharmacodynamics 

Necitumumab binds specifically to the extracellular domain of the epidermal growth factor receptor (EGFR) on cancer cells, preventing the binding of natural ligands and subsequent receptor activation. This inhibition blocks key signaling pathways involved in tumor cell proliferation, survival, and angiogenesis. Additionally, necitumumab triggers antibody-dependent cellular cytotoxicity (ADCC), which recruits immune cells to kill EGFR-expressing tumor cells. Together, these actions reduce tumor growth and promote cancer cell death. 

Pharmacokinetics 

Absorption 

Administered intravenously, providing 100% bioavailability. 

Distribution 

The volume of distribution is 7L. 

Metabolism 

Necitumumab is metabolized through proteolytic degradation into small peptides and amino acids, typical of monoclonal antibodies. 

Excretion and Elimination 

The half-life is 14 days.

Adminstartion

Necitumumab is administered by intravenous (IV) infusion. The infusion should be given over at least 90 minutes for the first dose. If the first infusion is well tolerated, subsequent infusions may be given over 60 minutes. 

Patient Information Leaflet

Generic Name: necitumumab 

Pronounced: NEH-sih-TOO-moo-mab 

Why do we use necitumumab?   

Necitumumab is primarily used in combination with chemotherapy for the treatment of metastatic squamous non-small cell lung cancer (NSCLC). It is specifically indicated for patients whose tumors express the epidermal growth factor receptor (EGFR) and is given alongside gemcitabine and cisplatin chemotherapy to improve survival outcomes in this aggressive type of lung cancer.