Dataset Information

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.

SUBMITTER: Lou E

PROVIDER: S-EPMC6295659 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Lou Emil E D'Souza Donna D Nelson Andrew C AC

Journal of the National Comprehensive Cancer Network : JNCCN 20170401 4

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 availab ...[more]

PMID: 28404754

Similar Datasets

Project description:BackgroundThe epidermal growth factor receptor (EGFR)/RAS/RAF/MEK/MAPK pathway is an important pathway in the carcinogenesis, invasion and metastasis of colorectal cancers (CRCs). We conducted a retrospective study to determine the prognostic values of EGFR expression and KRAS mutation in patients with metastatic CRC (mCRC) based on synchronous or metachronous status.MethodsFrom October 2002 to March 2012, 205 patients with mCRC were retrospectively analyzed; 98 were found to have metachronous mCRC while 107 were found to have synchronous mCRC. The EGFR expressions were determinate by IHC (immunohistochemistry) analysis and categorized 1+ (weak intensity), 2+ (moderate intensity), and 3+ (strong intensity). Genomic DNA was isolated from frozen primary CRC tissues and direct sequencing of KRAS was performed. The clinicopathological features of these mCRC patients were retrospectively investigated according to EGFR expression and KRAS mutation status. Moreover, we analyzed the prognostic values of EGFR expression and KRAS mutation among these patients.ResultsOf the 205 patients with mCRC, EGFR expression was analyzed in 167 patients, and positive EGFR expression was noted in 140 of those patients (83.8%). KRAS mutation was investigated in 205 patients and mutations were noted in 88 of those patients (42.9%). In patients with metachronous mCRC, positive EGFR expression was significantly correlated with well-and moderately-differentiated tumors (P=0.028), poorer disease-free survival (DFS) (P<0.001), and overall survival (OS) (P<0.001). Furthermore, positive EGFR expression was a significant independent prognostic factor of DFS (P=0.006, HR: 4.012, 95% CI: 1.130-8.445) and OS (P=0.028, HR: 3.090, 95% CI: 1.477-10.900) in metachronous mCRC patients. KRAS mutation status was not significantly related to DFS and OS of patients with metachronous mCRC; likewise, KRAS mutation status was not significantly different in the progression-free survival (PFS) and OS of patients with synchronous mCRC (all P>0.05).ConclusionsThe present study demonstrated that EGFR expression has prognostic value only for patients with metachronous mCRC. However, KRAS mutation did not have prognostic value in patients with metachronous or synchronous mCRC.

Dataset Information

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

Publications

Therapeutic Response of Metastatic Colorectal Cancer Harboring a <i>KRAS</i> Missense Mutation After Combination Chemotherapy With the EGFR Inhibitor Panitumumab.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets