Cetuximab

Cetuximab is a recombinant chimeric human/mouse IgG1 monoclonal antibody that competitively binds to epidermal growth factor receptor (EGFR) and competitively inhibits the binding of epidermal growth factor (EGF). EGFR is a member of the ErbB family of receptor tyrosine kinases found in both normal and tumour cells; it is responsible for regulating epithelial tissue development and homeostasis. EGFR has been implicated in various types of cancer, as it is often overexpressed in malignant cells and EGFR overexpression has been linked to more advanced disease and poor prognosis. EGFR is often mutated in certain types of cancer and serves as a driver of tumorigenesis. In vitro, cetuximab was shown to mediate anti-tumour effects in numerous cancer cell lines and human tumour xenografts.

Approved by the FDA in February 2004 under the brand name ERBITUX, cetuximab is used for the treatment of head and neck cancer and metastatic, KRAS wild-type colorectal cancer, and metastatic colorectal cancer with a BRAF V600E mutation. It has also been investigated in advanced colorectal cancer, EGFR-expressing non-small cell lung cancer (NSCLC), and unresectable squamous cell skin cancer. Cetuximab is administered via intravenous infusion and is used as monotherapy or in combination with other chemotherapies, including platinum agents, radiation therapy, leucovorin, fluorouracil, and irinotecan.

Cetuximab indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy. It is indicated for treating a recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with fluorouracil. It is indicated for recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

Cetuximab is also indicated for K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test in combination with FOLFIRI, a chemotherapy combination that includes leucovorin, fluorouracil, and irinotecan; in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy; or as monotherapy in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan.

Additionally, cetuximab is also indicated for metastatic colorectal cancer that is BRAF V600E mutation-positive (as determined by an FDA-approved test) in combination with encorafenib but only after prior therapy.

Cetuximab is not indicated for the treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown.