Impact of the Specific Mutation inKRASCodon 12 Mutated Tumors on Treatment Efficacy in Patients with Metastatic Colorectal Cancer Receiving Cetuximab-Based First-Line Therapy: A Pooled Analysis of Three Trials

Dominik P. Modest, Thomas Brodowicz, Sebastian Stintzing, Andreas Jung, Jens Neumann, Ruediger P. Laubender, Janja Ocvirk, Galina Kurteva, Zsuzsanna Papai, Regina Knittelfelder, Thomas Kirchner, Volker Heinemann (+1 others)
2012 Oncology  
ard ratio 0.66, range 0. 43-1.03). An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab. Conclusion: The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy. Introduction Kirsten-ras (KRAS) is a proto-oncogene encoding a small G protein. The KRAS protein is located at the inner cell membrane and has guanosine
more » ... osphatase (GTPase) activity. Extracellular binding of ligands to transmembrane receptors like the epidermal growth fac- Key Words Metastatic colorectal cancer ؒ KRAS mutation ؒ Codon 12 ؒ Cetuximab ؒ Anti-epidermal growth factor receptor Abstract Purpose: This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC). Patients: Overall, 119 patients bearing a KRAS mutation in codon 12 were evaluated. All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group (CECOG), AIO KRK-0104 or AIO KRK-0306 trials. Results: Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens. Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations (overall survival 23.3 vs. 14-18 months; haz-
doi:10.1159/000339534 pmid:22948721 fatcat:vapmc7hvcfcgrielmippnxwtze