Defective mismatch repair and benefit from bevacizumab for colon cancer: findings from NSABP C-08

J Natl Cancer Inst. 2013 Jul 3;105(13):989-92. doi: 10.1093/jnci/djt140.

Abstract

National Surgical Adjuvant Breast and Bowel Project protocol C-08 tested the worth of adding 1 year of bevacizumab to oxaliplatin-based standard adjuvant chemotherapy regimen in the treatment of stage II/III colon cancer. Although the overall result was negative, the possibility that a molecularly defined subset could benefit from bevacizumab cannot be ruled out. We performed post hoc Cox regression analyses to test for marker-by-treatment interactions for standard pathological features and survival analyses using the Kaplan-Meier method. All statistical tests were two-sided and considered statistically significant at the .05 level. Patients diagnosed with mismatch repair defective (dMMR) tumors derived statistically significant survival benefit from the addition of bevacizumab (hazard ratio [HR] = 0.52; 95% confidence interval [CI] = 0.29 to 0.94; P = .02) in contrast with no benefit in patients diagnosed with mismatch repair proficient tumors (HR = 1.03; 95% CI = 0.84 to 1.27; p = .78; P(interaction)= .04). Although a post hoc finding, this data suggests that a molecularly defined subset of colon cancer patients may derive clinical benefit from antiangiogenesis agents and underscores the need for independent validation in other clinical trials.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • DNA Mismatch Repair / drug effects*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Odds Ratio
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Proto-Oncogene Proteins B-raf / genetics
  • Treatment Failure
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Organoplatinum Compounds
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Oxaliplatin
  • Bevacizumab
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf