Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy? : Genetics in Medicine : Nature Publishing Group
Genetics in Medicine | EGAPP Recommendation Statement
Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy?
This recommendation statement is a product of the independent EGAPP Working Group. Although the Centers for Disease Control and Prevention (CDC) provides support to the EGAPP Working Group, including staff support in the preparation of this document, recommendations made by the EGAPP Working Group should not be construed as official positions of the CDC or the US Department of Health and Human Services.
- Genetics in Medicine
- (2013)
- doi:10.1038/gim.2012.184
- Received
- Accepted
- Published online
Clinical Considerations
Definitions used by EGAPP
- Analytic validity refers to a test’s ability to accurately and reliably measure the genotype or analyte of interest, in this case: codon 12 and 13 mutations in KRAS exon 2, the BRAF V600E mutation, variants in NRAS (codons 12, 13, and 61), and in PIK3CA (exon 9 and exon 20), and loss of PTEN and AKT protein expression.
- Clinical validity defines the ability of the test to accurately and reliably identify or predict the intermediate or final outcomes of interest, in this case: tumor response or overall response rate to cetuximab or panitumumab, progression-free survival, and overall survival. This is usually reported in terms of clinical sensitivity and specificity.
- Clinical utility defines the balance of benefits and harms associated with the use of the test in practice, including improvement in measurable clinical outcomes and usefulness/added value in clinical management and decision making compared with not using the test. In this case, clinical outcomes and usefulness/value added includes avoidance of treatment-related adverse events and/or ineffective therapy.
Patient population under consideration
These recommendations apply to all patients with mCRC who are being considered for treatment with cetuximab or panitumumab. This statement is neither intended for, nor applicable to, patients in adjuvant or neo-adjuvant settings.
Considerations for practice
- KRAS wild-type status has been considered necessary but not sufficient to achieve a clinical response from anti-EGFR therapy. Approximately 40–60% of patients with wild-type KRAS also fail to achieve a response with anti-EGFR treatment.
- The EWG recommends that testing for KRAS (exon 2; codons 12 and 13) should be provided to patients with mCRC who are candidates for anti-EGFR antibody therapy using either cetuximab or panitumumab.
- Several sources suggest that patients with metastatic CRC who test positive for KRAS (exon 2; codons 12 and 13) mutations should not be treated with cetuximab or panitumumab.1,2,3,4
- Oncogenic mutations in KRAS may be present in ~30–50% of CRC tumors.5
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