Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone

Clin Colorectal Cancer. 2008 May;7(3):184-90. doi: 10.3816/CCC.2008.n.024.


Background: Identifying predictive biomarkers is important to optimally treat patients. This analysis evaluated the association of K-ras, BRAF, and PIK3CA gene mutations with tumor resistance to panitumumab alone.

Patients and methods: From 3 phase II panitumumab metastatic colorectal cancer (mCRC) studies, 62 of 533 patient samples were available. Mutations were identified from genomic DNA by sequencing.

Results: Of the 62 samples, 24 (38.7%) harbored a K-ras mutation, and 38 (61.3%) were wild type. In the wild-type K-ras group, 11% of patients had a partial response (PR), 53% had stable disease (SD), and 37% had progressive disease (PD). In the mutant K-ras group, 21% of patients had SD, and 79% of patients had PD; there were no responses. The absence of a K-ras mutation was associated with response to panitumumab (PR vs. SD vs. PD; P = .0028). The hazard ratio for wild-type versus mutant K-ras was 0.4 (95% CI, 0.2-0.7) for progression-free survival and 0.5 (95% CI, 0.3-0.9) for overall survival. Four patients had a V600E BRAF mutation, and 2 patients had a PIK3CA mutation.

Conclusion: These data suggest that patients with mCRC with activating K-ras mutations are less likely to respond to panitumumab alone. The small sample size limits us from defining a predictive role of PIK3CA and BRAF mutations for panitumumab treatment.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Clinical Trials, Phase II as Topic
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / secondary
  • DNA, Viral / analysis
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Panitumumab
  • Proto-Oncogene Proteins / genetics*
  • Survival Rate
  • Treatment Outcome
  • ras Proteins / genetics*


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • DNA, Viral
  • Proto-Oncogene Proteins
  • Panitumumab
  • ras Proteins