KRAS and BRAF Testing and Colorectal Cancer
In 2009, the American Society of Clinical Oncology released its first Provisional Clinical Opinion recommending that all patients with CRC being considered for EGFR antagonists should be tested for KRAS gene mutations prior to the initiation of therapy. In addition, the National Comprehensive Cancer Network also updated its guideline recomending KRAS testing on primary tumor or metastasis as a pre-treatment workup for metastatic CRC patients, and also when KRAS gene is not mutated determine BRAF gene status.
Identifying patients who will benefit from certain treatment strategies is vital to ensuring better clinical outcomes. The presence of a KRAS mutation is highly predictive of a patient's non-responsiveness to the EGFR inhibitors Erbitux® (cetuximab) or Vetibix™ (panitumumab). The incidence of KRAS gene mutation in colorectal cancer (CRC) is approximately 35-45%. BRAF gene mutations also account for another 8-10% of patients failing to respond to anti-EGFR treatment and confirmed in multiple studies.1,2
BRAF mutation testing is also utilized to assist with the differentiation of microsatellite instability high (MSI-H) hereditary non-polyposis colon cancer (HNPCC) from sporadic MSI-H CRC. Microsatellite instability (MSI) is commonly detected in ~90% of patients with HNPCC and 15% of sporadic CRC. It is generally recommneded that patients at increased risk for Lynch syndrome undergo pre-screening with microsatellite instability anaylsis by immunohistochemistry.
- Hawkes E and Cunningham D (2010).Relationship Between Colorectal Cancer Biomarkers and Response to Epidermal Growth Factor Receptor Monoclonal Antibodies. J.Clin Oncol 29 5626-5628
- Roth et al. (2010) Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol.28(3):466-74