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?
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It has been suggested that patients with metastatic colorectal cancer (mCRC) whose tumors harbor certain mutations affecting EGFR pathway signaling are typically unresponsive to therapy with anti-EGFR antibodies (cetuximab and panitumumab). The EWG identified recent evidence reviews that have addressed this topic, and this recommendation statement is based on results of these reviews. In developing these recommendations the EWG considered evidence in the areas described below.
EGAPP Recommendation Statement: The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (EWG) found that, for patients with metastatic colorectal cancer (mCRC) who are being considered for treatment with cetuximab or panitumumab, there is convincing evidence to recommend clinical use of KRAS mutation analysis to determine which patients are KRAS mutation positive and therefore unlikely to benefit from these agents before initiation of therapy. The level of certainty of the evidence was deemed high, and the magnitude of net health benefit from avoiding potentially ineffective and harmful treatment, along with promoting more immediate access to what could be the next most effective treatment, is at least moderate.
The EWG found insufficient evidence to recommend for or against BRAF V600E testing for the same clinical scenario. The level of certainty for BRAF V600E testing to guide antiepidermal growth factor receptor (EGFR) therapy was deemed low. The EWG encourages further studies of the potential value of testing in patients with mCRC who were found to have tumors that are wild type (mutation negative) for KRAS to predict responsiveness to therapy.
The EWG found insufficient evidence to recommend for or against testing for mutations in NRAS, or PIK3CA, and/or loss of expression of PTEN or AKT proteins. The level of certainty for this evidence was low. In the absence of supporting evidence, and with consideration of other contextual issues, the EWG discourages the use of these tests in guiding decisions on initiating anti-EGFR therapy with cetuximab or panitumumab unless further evidence supports improved clinical outcomes
EGAPP RecommendationExternal (February 2013)
Evidence ReportExternal (May 2011)
CDC Summary of EGAPP Recommendation (May 2010)
Question 1: In patients with mCRC, can other EGFR-related testing improve (or lead to non-inferior) patient outcomes or decision making compared to not using additional testing?
Question 2: How well do each of these tests predict treatment effectiveness?
Question 3: How well do each of these tests predict important health outcomes?
Question 3: How well does UGT1A1 testing predict phenotypic markers (e.g., increased plasma SN-38 levels or decreased enzyme activity) and associated adverse drug reactions (e.g., diarrhea or neutropenia)?
Question 4: What are the potential harms to patients in using these tests to guide treatment decisions?
Why EGAPP Selected this Topic for Review:
Key Criteria: opportunity to use evidence review from another organization
Other Considerations: combined several evidence reviews to make recommendation