title: Therapeutic Response of Metastatic Colorectal Cancer Harboring aKRASMissense Mutation After Combination Chemotherapy With the EGFR Inhibitor Panitumumab.
abstract: Over the past decade, subset analyses of retrospective and prospective clinical studies have determined thatKRAS-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 theKRASoncogene has expanded significantly, and testing of allRASfamily genes has become more widely available in clinical laboratories. Expert consensus guidelines have recommended not using EGFR inhibitors in patients withKRAS-mutated tumors. However, with increasing identification of low-prevalence variants, it is conceivable that someRASmutations 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 ofKRAS, 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 thatKRASmutant tumors fail to respond to therapy with EGFR inhibitors, altering the paradigm of using this generalized approach.
authors.affiliation: Departments of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota
authors.forename: Emil
authors.initials: E
authors.lastname: Lou
authors.affiliation: Departments of Radiology, University of Minnesota, Minneapolis, Minnesota
authors.forename: Donna
authors.initials: D
authors.lastname: D'Souza
authors.affiliation: Departments of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Nelson
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D011905:Genes, ras; D005820:Genetic Testing; D006801:Humans; D061705:Image-Guided Biopsy; D008875:Middle Aged; D064847:Multimodal Imaging; D020125:Mutation, Missense; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000077544:Panitumumab; D066246:ErbB Receptors