Therapeutic response of metastatic colorectal cancer harboring a KRAS missense mutation after combination chemotherapy with the EGFR inhibitor panitumumab

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)427-432
Number of pages6
JournalJNCCN Journal of the National Comprehensive Cancer Network
Volume15
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Missense Mutation
Combination Drug Therapy
Epidermal Growth Factor Receptor
Colorectal Neoplasms
Guidelines
Therapeutics
Mutation
Carcinoembryonic Antigen
Oncogenes
Codon
Colonic Neoplasms
Neoplasms
Biomarkers
Monoclonal Antibodies
panitumumab
Prospective Studies
Drug Therapy
Genes

PubMed: MeSH publication types

  • Case Reports
  • Journal Article

Cite this

@article{f906ce9693064c4394a53169505a5f68,
title = "Therapeutic response of metastatic colorectal cancer harboring a KRAS missense mutation after combination chemotherapy with the EGFR inhibitor panitumumab",
abstract = "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.",
author = "Emil Lou and D'Souza, {Donna L} and Nelson, {Andrew C}",
year = "2017",
month = "4",
day = "1",
doi = "10.6004/jnccn.2017.0043",
language = "English (US)",
volume = "15",
pages = "427--432",
journal = "Journal of the National Comprehensive Cancer Network : JNCCN",
issn = "1540-1405",
publisher = "Cold Spring Publishing LLC",
number = "4",

}

TY - JOUR

T1 - Therapeutic response of metastatic colorectal cancer harboring a KRAS missense mutation after combination chemotherapy with the EGFR inhibitor panitumumab

AU - Lou, Emil

AU - D'Souza, Donna L

AU - Nelson, Andrew C

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85017535183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017535183&partnerID=8YFLogxK

U2 - 10.6004/jnccn.2017.0043

DO - 10.6004/jnccn.2017.0043

M3 - Article

C2 - 28404754

AN - SCOPUS:85017535183

VL - 15

SP - 427

EP - 432

JO - Journal of the National Comprehensive Cancer Network : JNCCN

JF - Journal of the National Comprehensive Cancer Network : JNCCN

SN - 1540-1405

IS - 4

ER -