Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Kaczirek, K; Ciuleanu, TE; Vrbanec, D; Marton, E; Messinger, D; Liegl-Atzwanger, B; Wrba, F; Knittelfelder, R; Lindner, E; Zielinski, CC; Streubel, B; Brodowicz, T.
FOLFOX4 Plus Cetuximab for Patients With Previously Untreated Metastatic Colorectal Cancer According to Tumor RAS and BRAF Mutation Status: Updated Analysis of the CECOG/CORE 1.2.002 Study.
Clin Colorectal Cancer. 2015; 14(2):91-98
Doi: 10.1016/j.clcc.2014.12.003
Web of Science
PubMed
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FullText_MUG
- Co-authors Med Uni Graz
- Liegl-Atzwanger Bernadette
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- Abstract:
- This updated analysis of the CECOG/CORE 1.2.002 study investigated the association between clinical outcome and RAS and BRAF mutations in metastatic colorectal cancer (mCRC) patients treated with FOLFOX4 plus cetuximab. Available DNA samples from CECOG/CORE 1.2.002 study patients with KRAS exon 2 wild type (wt) (at codons 12 and 13) tumors were screened for mutations at other loci in the KRAS and NRAS (RAS) coding regions by Sanger sequencing, and for BRAF codon 600 mutations by Sanger sequencing and pyrosequencing. Clinical outcome was compared among different mutation subgroups. Of 152 KRAS wt mCRC patients, 148 were evaluable for RAS and BRAF mutation status. Eleven RAS mutations were detected in 10 patients' tumors (7%). BRAF mutations were detected in 14 patients' tumors (9%). RAS and BRAF tumor mutations were mutually exclusive. Compared with patients with RAS wt/BRAF wt tumors (n = 124; median overall survival, 28.5 months), those with RAS mutations (n = 10; median, 16.3 months; hazard ratio, 0.43; 95% confidence interval, 0.20-0.89; P = .020) or BRAF mutations (n = 14; median, 11.7 months; hazard ratio, 0.23; 95% confidence interval, 0.12-0.41; P < .0001) had worse overall survival, which remained significant (P < .04) when adjusting for differences in baseline characteristics among the mutation subgroups. These findings support those from recent studies that RAS and BRAF mutations are associated with poor outcome in patients receiving an epidermal growth factor receptor-targeted monoclonal antibody in combination with oxaliplatin-based chemotherapy. Furthermore, mutation testing should not only include RAS codons 12 and 13 but should also be extended to the entire coding regions. Copyright © 2015 Elsevier Inc. All rights reserved.
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