Reference Detail

Ref Type Journal Article
PMID (28404754)
Authors Lou E, D'Souza D, Nelson AC
Title Therapeutic Response of Metastatic Colorectal Cancer Harboring a KRAS Missense Mutation After Combination Chemotherapy With the EGFR Inhibitor Panitumumab.
Journal Journal of the National Comprehensive Cancer Network : JNCCN
Vol 15
Issue 4
Date 2017 Apr
URL
Abstract Text Over the past decade, subset analyses of retrospective and prospective clinical studies have determined that KRAS-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 KRAS oncogene has expanded significantly, and testing of all RAS family genes has become more widely available in clinical laboratories. Expert consensus guidelines have recommended not using EGFR inhibitors in patients with KRAS-mutated tumors. However, with increasing identification of low-prevalence variants, it is conceivable that some RAS 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 KRAS, 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 KRAS mutant tumors fail to respond to therapy with EGFR inhibitors, altering the paradigm of using this generalized approach.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
A59T missense unknown KRAS A59T lies within a GTP binding region of the Kras protein (UniProt.org). A59T has been identified in the scientific literature (PMID: 26924569, PMID: 28404754), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Mar 2019).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KRAS A59T colon cancer predicted - sensitive Fluorouracil + Irinotecan + Leucovorin + Panitumumab Case Reports/Case Series Actionable In a clinical case study, a colon cancer patient harboring KRAS A59T demonstrated sensitivity to the combination treatment of Vectibix (panitumumab) and FOLFIRI, which resulted in an objective response of a 36% decrease according to RECIST (PMID: 28404754). 28404754