Therapeutic Response of Metastatic Colorectal Cancer Harboring a Missense Mutation After Combination Chemotherapy With the EGFR Inhibitor Panitumumab.

Over the past decade, subset analyses of retrospective and prospective clinical studies have determined that -mutated metastatic colorectal cancers do not respond effectively to inhibition of epidermal growth factor receptor (EGFR) with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. Within the past few years, the scope of tested variants in the oncogene has expanded significantly, and testing of all family genes has become more widely available in clinical laboratories. Expert consensus guidelines have recommended not using EGFR inhibitors in patients with -mutated tumors. However, with increasing identification of low-prevalence variants, it is conceivable that some mutations do not provide equivalent resistance to EGFR inhibition compared with the most prevalent mutations at codons 12, 13, and 61. This report describes a case of a patient with metastatic colon cancer harboring the p.A59T variant of , with objective radiographic response (36% decrease per RECIST 1.1) and carcinoembryonic antigen biomarker response to panitumumab therapy given with FOLFIRI chemotherapy. We propose that A59T represents one potential exception to the guidelines that mutant tumors fail to respond to therapy with EGFR inhibitors, altering the paradigm of using this generalized approach.