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

Abstract

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.

• Authors: Daniel J Freeman, Todd Juan, Maureen Reiner, J Randolph Hecht, Neal J Meropol, Jordan Berlin, Edith Mitchell, Ildiko Sarosi, Robert Radinsky, Rafael G Amado
• Journal: Clinical colorectal cancer (Clin Colorectal Cancer) Vol. 7 Issue 3 Pg. 184-90 (May 2008) ISSN: 1533-0028 [Print] United States
• PMID: 18621636 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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, genetics, secondary)
• DNA, Viral (analysis)
• Disease Progression
• Female
• Humans
• Male
• Middle Aged
• Mutation
• Panitumumab
• Proto-Oncogene Proteins (genetics)
• Survival Rate
• Treatment Outcome
• ras Proteins (genetics)