scholarly journals KRAS Codon 12 Mutation is Associated with More Aggressive Invasiveness in Synchronous Metastatic Colorectal Cancer (mCRC): Retrospective Research

2020 ◽  
Vol Volume 13 ◽  
pp. 12601-12613
Author(s):  
Kang He ◽  
Yajing Wang ◽  
Yuejiao Zhong ◽  
Xiaohua Pan ◽  
Lixiang Si ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kras Codon

Mutant KRAS Codon 12 and 13 Alleles in Patients With Metastatic Colorectal Cancer: Assessment As Prognostic and Predictive Biomarkers of Response to Panitumumab

2013 ◽  
Vol 31 (6) ◽  
pp. 759-765 ◽  
Author(s):  
Marc Peeters ◽  
Jean-Yves Douillard ◽  
Eric Van Cutsem ◽  
Salvatore Siena ◽  
Kathy Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Retrospective Analysis ◽  
Human Monoclonal Antibody ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Wild Type ◽  
Codon 12 And 13 ◽  
Kras Codon

Purpose Panitumumab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has demonstrated significant improvements in progression-free survival (PFS) in patients with wild-type KRAS metastatic colorectal cancer (mCRC) in studies 20050203 (first line), 20050181 (second line), and 20020408 (monotherapy). Mutations in KRAS codons 12 and 13 are recognized biomarkers that predict lack of response to anti-EGFR antibody therapies. This retrospective analysis of three randomized phase III studies assessed the prognostic and predictive impact of individual mutant KRAS codon 12 and 13 alleles. Patients and Methods Patients were randomly assigned 1:1 to FOLFOX4 (infusional fluorouracil, leucovorin, and oxaliplatin) in study 20050203, FOLFIRI (fluorouracil, leucovorin, and irinotecan) in study 20050181, or best supportive care in study 20020408 with or without panitumumab 6.0 mg/kg once every 2 weeks. In all, 441 (20050203), 486 (20050181), and 126 (20020408) patients with mutant KRAS codon 12 or 13 alleles were included in the analysis. Results No mutant KRAS allele in patients treated on the control arm emerged as a consistent prognostic factor for PFS or overall survival (OS). In addition, no mutant KRAS allele was consistently identified as a predictive factor for PFS or OS in patients receiving panitumumab treatment. Significant interactions for individual mutant KRAS alleles were observed only in study 20050203 with G13D negatively and G12V positively associated with OS in the panitumumab-containing arm. Pooled analysis indicated that only G12A was associated with a negative predictive effect on OS. Conclusion In this retrospective analysis, results across three treatment regimens suggest that patients with mutant KRAS codon 12 or 13 mCRC tumors are unlikely to benefit from panitumumab therapy. Currently, panitumumab therapy should be limited to patients with wild-type KRAS mCRC.

Mutations in NRAS codon 61, KRAS codon 146, and BRAF V600E as prognostic factors in patients who received anti-EGFR antibody for metastatic colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14126-e14126
Author(s):  
Naoki Takahashi ◽  
Yasuhide Yamada ◽  
Hirokazu Taniguchi ◽  
Kohei Akiyoshi ◽  
Yoshitaka Honma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Poor Prognosis ◽  
Tumor Response ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Antibody Treatment ◽  
Kras Codon ◽  
Egfr Antibody ◽  
Codon 61

e14126 Background: Previous studies showed that gene mutations (NRAS, BRAF, PIK3CA) are associated with a poor prognosis or resistance of anti-EGFR antibody in metastatic colorectal cancer (mCRC) patients with wild type (WT) of KRAS codon 12/13 (KRAS-WT). However the significance of these biomarkers has not been clarified. In addition, EGFR immunohistochemistry (IHC) and EGFR gene amplification to evaluate the efficacy of anti-EGFR antibody treatment has not been reported for mCRC. Methods: We evaluated tumor response and survival in patients who received anti-EGFR antibody by mutation analysis of KRAS, NRAS, BRAF, and PIK3CA in KRAS-WT patients with mCRC. Tumor DNA samples are obtained from patients treated in our hospital with anti-EGFR antibody between August 2008 and August 2011. Results: A total of 117 patients were enrolled in this analysis, including 100 KRAS-WT patients. Seventy-one patients (60.7%) were all WT for KRAS, NRAS, BRAF, and PIK3CA, and 46 patients (39.3%) had at least 1 mutation or had insufficient DNA samples to analyze. Mutations of KRAS codon 61 (2 patients), KRAS codon 146 (5), BRAF V600E (2), PIK3CA exon9 (8), NRAS codon 12/13 (2), and NRAS codon 61 (5) were detected. No patients had a mutation of PIK3CA exon 20. Patients with at least 1 mutation had no response. Mutations of NRAS codon 61, KRAS codon 146, and BRAF V600E were associated with a shorter progression free survival (PFS) compared with all WT patients (p=0.049, p=0.004, p=0.036, respectively). Twelve patients (12% of KRAS-WT patients) with a mutation of NRAS codon 61, KRAS codon146, and BRAF V600E had poor prognosis compared with the other KRAS-WT patients (PFS, 6.4 vs 2.0 months, p<0.001; overall survival (OS), 13.7 vs 7.9 months, p=0.012). In all WT patients, moderate to strong EGFR IHC was associated with a better response rate than negative and weak IHC (p=0.046). Conclusions: Mutations of NRAS codon 61, KRAS codon 146, and BRAF V600E could be a strong prognostic factor of anti-EGFR antibody in patients with mCRC. Combination of IHC and DISH of EGFR could identify patients with a tumor response to anti-EGFR antibody in patients that are all WT for KRAS, NRAS, BRAF, and PIK3CA.

scholarly journals Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

2017 ◽  
Author(s):  
Bingjun Bai ◽  
Lina Shan ◽  
Binbin Xie ◽  
Xuefeng Huang ◽  
Weifang Mao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Chinese Patients ◽  
Poor Survival ◽  
Kras Codon

scholarly journals P-225 KRAS codon 12 and 13 mutations in metastatic colorectal cancer: Predictive marker in first-line bevacizumab-based chemotherapy

2020 ◽  
Vol 31 ◽  
pp. S163-S164
Author(s):  
T. Cunha Pereira ◽  
F. Salgueiro ◽  
A. Monteiro ◽  
R. Félix Soares ◽  
F. Macedo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Predictive Marker ◽  
First Line ◽  
Codon 12 And 13 ◽  
Kras Codon
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