Anti-EGF Receptor-Based Conversion Chemotherapy in RAS Wild-Type Colorectal Cancer Patients: Impact on Survival and Resection Rates

Digestion. 2018;98(4):263-269. doi: 10.1159/000490888. Epub 2018 Aug 21.

Abstract

Background: Initially unresectable colorectal liver metastases can become resectable after chemotherapy. Combination chemotherapy with epidermal growth factor receptor (EGFR) antibodies has shown consistent high response rates in patients with all rat sarcoma (RAS) wild-type tumors.

Methods: Out of a cohort of 424 patients with metastatic colorectal cancer, we identified 30 patients with initially unresectable Kirsten RAS (KRAS) exon 2 wild-type colorectal liver metastases who received neoadjuvant chemotherapy with anti-EGFR agents between January 2008 and February 2014. In all patients, extended RAS analysis (KRAS and NRAS exon 3 codon 59/61 and exon 4 codon 117/146) was carried out retrospectively.

Results: RAS mutation analysis identified further KRAS mutations in 4/30 patients (13.3%). In none of these 4 patients a R0 resection was achieved. In contrast, 15/26 (57.7%) RAS wild-type patients were R0 resected. Median overall survival was > 63.3 months in R0-resected patients versus 30.0 months in those with a R1 or R2 resection (HR 0.23; [95% CI 0.10-0.75; p = 0.008).

Conclusion: Our data suggest that a RAS wild-type and a R0 resection are the strongest predictors for overall survival.

Keywords: Chemotherapy; Colorectal cancer; RAS wild type; Resection.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • DNA Mutational Analysis / methods
  • ErbB Receptors / antagonists & inhibitors
  • Exons / genetics
  • Female
  • GTP Phosphohydrolases / genetics
  • Hepatectomy / statistics & numerical data*
  • Humans
  • Liver / drug effects
  • Liver / surgery
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary
  • Liver Neoplasms / therapy*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation
  • Neoadjuvant Therapy / methods
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Retrospective Studies
  • Survival Analysis
  • Tumor Burden / drug effects*
  • Tumor Burden / genetics

Substances

  • KRAS protein, human
  • Membrane Proteins
  • EGFR protein, human
  • ErbB Receptors
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Proto-Oncogene Proteins p21(ras)