Effect of <it>KRAS</it> codon13 mutations in patients with advanced colorectal cancer (advanced CRC) under oxaliplatin containing chemotherapy. Results from a translational study of the AIO colorectal study group

• Main Authors: Reinacher-Schick Anke, Schulmann Karsten, Modest Dominik P, Bruns Nina, Graeven Ulrich, Jaworska Malgorzata, Greil Richard, Porschen Rainer, Arnold Dirk, Schmiegel Wolff, Tannapfel Andrea
• Format: Article
• Language: English
• Published: BMC 2012-08-01
• Series: BMC Cancer
• Subjects: Codon 13 mutation; Colorectal cancer; <it>KRAS</it>; Oxaliplatin; Prognosis
• Online Access: http://www.biomedcentral.com/1471-2407/12/349

<p>Abstract</p> <p>Background</p> <p>To evaluate the value of <it>KRAS</it> codon 13 mutations in patients with advanced colorectal cancer (advanced CRC) treated with oxaliplatin and fluoropyrimidines.</p> <p>Methods</p> <p>Tumor specimens from 201 patients with advanced CRC from a randomized, phase III trial comparing oxaliplatin/5-FU vs. oxaliplatin/capecitabine were retrospectively analyzed for <it>KRAS</it> mutations. Mutation data were correlated to response data (Overall response rate, ORR), progression-free survival (PFS) and overall survival (OS).</p> <p>Results</p> <p>201 patients were analysed for <it>KRAS</it> mutation (61.2% males; mean age 64.2 ± 8.6 years). <it>KRAS</it> mutations were identified in 36.3% of tumors (28.8% in codon 12, 7.4% in codon 13). The ORR in codon 13 patients compared to codon 12 and wild type patients was significantly lower (p = 0.008). There was a tendency for a better overall survival in <it>KRAS</it> wild type patients compared to mutants (p = 0.085). PFS in all patients was not different in the three <it>KRAS</it> genetic groups (p = 0.72). However, we found a marked difference in PFS between patients with codon 12 and 13 mutant tumors treated with infusional 5-FU versus capecitabine based regimens.</p> <p>Conclusions</p> <p>Our data suggest that the type of <it>KRAS</it> mutation may be of clinical relevance under oxaliplatin combination chemotherapies without the addition of monoclonal antibodies in particular when overall response rates are important.</p> <p>Trial registration number</p> <p>2002-04-017</p>