KRAS status and outcome of liver resection after neoadjuvant chemotherapy including bevacizumab

Br J Surg. 2012 Nov;99(11):1575-82. doi: 10.1002/bjs.8909.

Abstract

Background: The prognostic value of KRAS mutation in patients with colorectal cancer liver metastases (CLM) receiving neoadjuvant chemotherapy including bevacizumab before liver resection is unclear.

Methods: The KRAS and BRAF status of resected CLM was assessed in prospectively studied patients. Mutations were correlated with recurrence-free and overall survival. Only patients with remaining vital tumour cells in the resected specimen and those without disease progression were analysed; those with progressive disease did not undergo resection.

Results: A total of 60 patients were enrolled. Fifteen (25 per cent) had a KRAS mutation, but none of the 60 patients had a BRAF mutation. The radiological response to neoadjuvant chemotherapy including bevacizumab, assessed according to the Response Evaluation Criteria In Solid Tumours, was partial in 52 patients (87 per cent) and the remaining eight had stable disease. The partial response rate was similar in patients with a KRAS mutation and those with the wild-type gene (12 of 15 versus 40 of 45 patients; P = 0·400). KRAS mutation had a negative prognostic effect on recurrence-free survival (hazard ratio (HR) 2·48, 95 per cent confidence interval 1·26 to 4·89; P = 0·009) and overall survival (HR 3·51, 1·30 to 9·45; P = 0·013).

Conclusion: This study provided further evidence for the prognostic importance of KRAS status in terms of recurrence-free and overall survival. Neoadjuvant chemotherapy including bevacizumab elicited a response, irrespective of KRAS status, in this selected group of patients with CLM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Bevacizumab
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / genetics*
  • Female
  • Genes, ras / genetics*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / therapy
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Recurrence, Local / genetics
  • Prospective Studies
  • Proto-Oncogene Proteins B-raf / genetics*

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf