Meta-analysis Comparing the Efficacy of anti-EGFR Monoclonal Antibody Therapy Between KRAS G13D and Other KRAS Mutant Metastatic Colorectal Cancer Tumours

Eur J Cancer. 2016 Mar;55:122-30. doi: 10.1016/j.ejca.2015.11.025. Epub 2016 Jan 23.

Abstract

Background: Metastatic colorectal cancer (mCRC) tumours harbouring a RAS mutation are associated with a lack of treatment benefit from anti-EGFR monoclonal antibodies (mAbs). However, observational evidence has led to speculation that mCRC patients with KRAS G13D mutant (MT) tumours may derive a benefit from treatment with anti-EGFR mAbs.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate whether the efficacy of anti-EGFR mAbs for mCRC differs between tumours harbouring a KRAS G13D mutation (KRAS G13D) and KRAS mutations other than G13D (other KRAS MT).

Results: Eight RCTs (n = 5967) met the inclusion criteria for assessment of both overall survival (OS) and progression-free survival (PFS). For other KRAS MT the hazard ratio for OS benefit with addition of anti-EGFR mAb therapy was 1.06 (95% confidence interval [CI]; 0.96, 1.17), compared to 1.08 (95% CI; 0.73, 1.60) for KRAS G13D [test for interaction p=0.99]. In contrast, the hazard ratio for KRAS wild-type (WT) tumours was 0.85 (95% CI; 0.76, 0.95). Regarding PFS benefit with anti-EGFR mAbs, the hazard ratio was 1.07 (95% CI; 0.92, 1.26) for other KRAS MT, 0.96 (95% CI; 0.73, 1.27) for KRAS G13D, and 0.68 (95% CI; 0.54, 0.85) for KRAS WT. Again, the test for interaction (p=0.46) demonstrated no significant difference in PFS benefit for anti-EGFR mAb therapy between KRAS G13D and other KRAS MT.

Conclusion: This meta-analysis demonstrates no significant difference between KRAS G13D and other KRAS MT tumours in terms of treatment benefit from anti-EGFR mAbs for mCRC.

Keywords: KRAS G13D mutation; anti-EGFR monoclonal antibodies; metastatic colorectal cancer; predictive biomarkers..

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / immunology
  • ErbB Receptors / metabolism
  • Genetic Predisposition to Disease
  • Humans
  • Mutation*
  • Neoplasm Metastasis
  • Phenotype
  • Proportional Hazards Models
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • KRAS protein, human
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)