Distinguishing Features of Cetuximab and Panitumumab in Colorectal Cancer and Other Solid Tumors

Abstract

Cetuximab and panitumumab are two distinct monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR), and both are widely used in combination with chemotherapy or as monotherapy to treat patients with RAS wild-type metastatic colorectal cancer. Although often considered interchangeable, the two antibodies have different molecular structures and can behave differently in clinically relevant ways. More specifically, as an immunoglobulin (Ig) G1 isotype mAb, cetuximab can elicit immune functions such as antibody-dependent cell-mediated cytotoxicity involving natural killer cells, T-cell recruitment to the tumor, and T-cell priming via dendritic cell maturation. Panitumumab, an IgG2 isotype mAb, does not possess these immune functions. Furthermore, the two antibodies have different binding sites on the EGFR, as evidenced by mutations on the extracellular domain that can confer resistance to one of the two therapeutics or to both. We consider a comparison of the properties of these two antibodies to represent a gap in the literature. We therefore compiled a detailed, evidence-based educational review of the known molecular, clinical, and functional differences between the two antibodies and concluded that they are distinct therapeutic agents that should be considered individually during treatment planning. Available data for one agent can only partly be extrapolated to the other. Looking to the future, the known immune activity of cetuximab may provide a rationale for this antibody as a combination partner with investigational chemotherapy plus immunotherapy regimens for colorectal cancer.

The Protective Role of Decorin in Hepatic Metastasis of Colorectal Carcinoma

“…Patients with colon cancer were among the first major beneficiaries of the introduction of targeted therapy, mainly because of the well-known molecular mechanisms responsible for the malignant phenotype [ 72 ]. At present, EGFR inhibitors such as cetuximab (Erbitux) and panitumumab (Vectibix) are widely used in the targeted therapy of CRC [ 73 ]. Decorin is known to effectively block the activity of EGFR but also of VEGFR, PDGFR, Met and Raf kinases.…”

The Molecular Mechanisms That Underlie the Immune Biology of Anti-drug Antibody Formation Following Treatment With Monoclonal Antibodies

“…Other mAbs in this category are omalizumab, an anti-IgE mAb that is used to treat patients with allergic asthma ( 9 ), palivizumab which targets an epitope in the A antigenic site of the F protein of the respiratory syncytial virus (RSV) ( 10 ), and bezlotoxumab which binds and neutralizes Clostridium difficile toxin B ( 11 ). Some mAbs, such as cetuximab and panitumumab ( 12 ), target the epidermal growth factor receptor (EGFR) which is overexpressed in a number of cancers. In recent years, checkpoint inhibitor mAbs were also developed to manipulate anti-tumor T-cell responses, like the anti-PD-1 nivolumab that is used to treat melanoma and non-small cell lung cancer ( 13 ).…”

Targeted Molecular Therapies in the Treatment of Esophageal Adenocarcinoma, Are We There Yet?

“…Cetuximab and panitumumab are monoclonal antibodies directed against EGFR and both are currently FDA approved for the treatment of KRAS -wild type metastatic colorectal cancer [ 50 ]. A recent phase III clinical trial evaluated the utility of cetuximab in patients with locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma.…”