Significance of KRAS mutation in patients receiving mFOLFOX6 with or without bevacizumab for metastatic colorectal cancer

Hepatogastroenterology. 2014 Nov-Dec;61(136):2222-6.

Abstract

Background/aims: KRAS mutation is an important prognostic factor for patients with metastatic colorectal cancer receiving anti-epidermal growth factor receptor therapy. However, the influence of KRAS mutation on the response to mFOLFOX6 ± bevacizumab remains unclear.

Methodology: We retrospectively analyzed 49 patients who received modified FOLFOX6 (mFOLFOX6) ± bevacizumab as first-line therapy. Genetic analysis showed that 30 patients had wild-type (WT) KRAS and 19 patients hadKRAS mutations (MT). These two groups were compared with regard to the response rate (RR), progression-free survival (PFS), and overall survival (OS).

Results: The RR was not significantly different between the WT and MT groups, but PFS and OS were significantly better in the WT group than the MT group (PFS: 11.8 months vs. 8.7 months, p<0.01; OS: 37.8 months vs. 29.3 months, p<0.0385). A similar analysis of 27 patients who were treated with mFOLFOX6 + bevacizumab showed a better prognosis for WT patients. Multivariate analysis also revealed that KRAS mutation was an independent factor with a significant relation to PFS.

Conclusions: These results suggest that KRAS mutation may be a useful prognostic marker for patients with metastatic colorectal cancer receiving mFOLFOX6 ± bevacizumab therapy, especially for patients treated with mFOLFOX6 + bevacizumab.

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis
  • Organoplatinum Compounds / administration & dosage
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Retrospective Studies
  • ras Proteins / genetics*

Substances

  • Antibodies, Monoclonal, Humanized
  • KRAS protein, human
  • Organoplatinum Compounds
  • Proto-Oncogene Proteins
  • Bevacizumab
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol