title: The influence of KRAS and BRAF mutations on the efficacy of cetuximab-based first-line therapy of metastatic colorectal cancer: an analysis of the AIO KRK-0104-trial.
abstract: Our study investigated the impact of specific KRAS mutations and BRAF mutation on progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated within the AIO KRK-0104-trial as first-line therapy. In total, 146 (of 185) patients were included in this analysis. Seventy-nine patients presented with KRAS/BRAF wild-type (wt), 41 patients with a KRAS codon 12 and nine patients with a KRAS codon 13 mutation. Seventeen patients presented a BRAF-mutated tumor. The patients of our study were treated with CAPIRI/CAPOX plus cetuximab. Major differences regarding PFS and OS were observed depending on the mutation of the tumor. PFS was 8 months in patients with wt-tumors, 5.8 months with codon 12-mutated, 9.9 months with codon 13-mutated and 4.2 months with BRAF-mutated tumors. OS was 23.5 months in patients with wt-tumors, 18.9 months with codon 12-mutated, 26.2 months with codon 13-mutated and 13.0 months with BRAF-mutated tumors. Although the conventional separation of patients with KRAS wild-type versus KRAS mutant tumors did not have a significant impact on outcome parameters in the AIO KRK 0104-trial, this analysis demonstrates that markedly differing results are obtained when subtypes of KRAS and BRAF mutation are taken into account.
authors.affiliation: Department of Medicine III, University of Munich, Munich, Germany. dominik.modest@med.uni-muenchen.de
authors.forename: D P
authors.initials: DP
authors.lastname: Modest
authors.forename: A
authors.initials: A
authors.lastname: Jung
authors.forename: N
authors.initials: N
authors.lastname: Moosmann
authors.forename: R P
authors.initials: RP
authors.lastname: Laubender
authors.forename: C
authors.initials: C
authors.lastname: Giessen
authors.forename: C
authors.initials: C
authors.lastname: Schulz
authors.forename: M
authors.initials: M
authors.lastname: Haas
authors.forename: J
authors.initials: J
authors.lastname: Neumann
authors.forename: S
authors.initials: S
authors.lastname: Boeck
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
authors.forename: V
authors.initials: V
authors.lastname: Heinemann
authors.forename: S
authors.initials: S
authors.lastname: Stintzing
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000068818:Cetuximab