Panitumumab: Targeting EGFR in Colorectal Cancer

Panitumumab is a fully human monoclonal antibody specifically designed to target the epidermal growth factor receptor (EGFR). EGFR plays a crucial role in cell growth and survival, especially in cancer cells. Panitumumab is manufactured by Amgen and was originally developed by Abgenix Inc.

Mechanism of Action: Panitumumab works by binding to the extracellular domain of EGFR, preventing its activation. By doing so, it halts the cascade of intracellular signals dependent on this receptor. Essentially, Panitumumab inhibits the growth and survival of tumors expressing EGFR.

Clinical Applications:

• Metastatic Colorectal Cancer: Panitumumab was approved by the U.S. Food and Drug Administration (FDA) for the treatment of EGFR-expressing metastatic colorectal cancer with disease progression despite prior treatment.

• Predictive Biomarker: Panitumumab was the first monoclonal antibody to demonstrate the use of KRAS as a predictive biomarker. It does not work in patients who have KRAS or NRAS mutations.

Adverse Effects:

• Skin Rash: Often, skin rash appears in sun-exposed parts of the body, such as the face or chest. Oral antibiotics or topical steroid creams may be needed for worsening skin rash.

• Ocular Toxicity: Keratitis (inflammation of the cornea) was observed in 16% of patients on panitumumab, often necessitating discontinuation of therapy.

• Pulmonary Fibrosis: Rarely, panitumumab has caused very serious lung disease.

Pharmacology:

• EGFR Inhibition: Panitumumab binds to the extracellular domain of EGFR, preventing its activation and downstream signaling.

• Half-Life: The elimination half-life of panitumumab is approximately 9.4 days.

Panitumumab offers a targeted approach to treating metastatic colorectal cancer by inhibiting EGFR. Its association with skin rash and ocular toxicity underscores the need for careful monitoring. Despite challenges, it remains a valuable tool in cancer therapy.