Association between KRAS codon 13 mutations and clinical response to anti-EGFR treatment in patients with metastatic colorectal cancer: results from a meta-analysis

Cancer Chemother Pharmacol. 2013 Jan;71(1):265-72. doi: 10.1007/s00280-012-2005-9. Epub 2012 Oct 23.


Purpose: To comparatively evaluate whether metastatic colorectal cancer (mCRC) patients with KRAS codon 13 mutations (codon 13 muts) can benefit from anti-EGFR treatment.

Methods: We performed a meta-analysis of relevant studies. Systematic searches of the PubMed, Embase, and Cochrane databases, as well as ASCO conference papers up to July 30, 2012, were retrieved, and the authors of included studies were contacted to obtain more individual data. Fixed effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary study end points were the overall response rate (ORR). Secondary end points were progress-free survival (PFS) and overall survival (OS).

Results: A total of 7 studies were included in the final meta-analysis, consisting of 2,802 mCRC patients, 1,679 of whom were treated with anti-EGFR monoclonal antibodies. The ORR of mCRC patients with codon 13 mutation was 25.2 % (29/115), compared to 17.6% (98/558) for other KRAS mutations (other mut) and 42.6% (429/1,006) for KRAS WT patients. The overall pooled RR for ORRs of codon 13 mut versus other mut was 1.52 (95% CI 1.10-2.09, P = 0.003), whereas the pooled RR for codon 13 mut versus WT was 0.61 (95% CI 0.45-0.83, P = 0.002). The pooled progression-free survival (PFS) times were 6.4 months for codon 13 mut, 4.1 months for other mut, and 6.6 months for WT, whereas the pooled OS durations were 14.6, 11.8, and 17.3 months, respectively. Subgroup analysis was conducted on the basis of the line of treatment, anti-EGFR drug, study design, and detection method, respectively. The results implicated that KRAS codon 13 mut patients gain more benefit from Cetuximab in further line treatment.

Conclusions: Metastatic colorectal cancer patients with KRAS codon 13 mutations demonstrate a greater clinical response to anti-EGFR treatment than patients with other KRAS mutations.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Codon
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • ErbB Receptors / immunology
  • Humans
  • Mutation
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Survival Rate
  • Treatment Outcome
  • ras Proteins / genetics*


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