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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
Author(s) -
Modest D.P.,
Jung A.,
Moosmann N.,
Laubender R.P.,
Giessen C.,
Schulz C.,
Haas M.,
Neumann J.,
Boeck S.,
Kirchner T.,
Heinemann V.,
Stintzing S.
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26467
Subject(s) - kras , cetuximab , colorectal cancer , medicine , oncology , mutation , cancer , cancer research , biology , genetics , gene
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.