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 cance
