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

Int J Cancer. 2012 Aug 15;131(4):980-6. doi: 10.1002/ijc.26467. Epub 2011 Nov 17.


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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use*
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • Genes, ras*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins B-raf / genetics*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • ErbB Receptors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Cetuximab