Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by<i>KRAS</i>Mutations in Advanced Colorectal Cancer

Dahabreh, Issa J; Terasawa, Teruhiko; Castaldi, Peter J.; Trikalinos, Thomas A

doi:10.7326/0003-4819-154-1-201101040-00006

Cited by 158 publications

(160 citation statements)

References 89 publications

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“…9,11,19,[23][24][25] Although none of the reviews on which this recommendation statement is based was commissioned by EGAPP, three EWG members provided expert guidance during the course of one of these systematic reviews 9 as members of a technical expert panel.…”

Section: Methodsmentioning

confidence: 99%

“…23 A summary of the section of this assessment that addressed KRAS testing for anti-EGFR therapy in CRC was published by Evidence-Based Practice Center investigators in January 2011. 24 In December 2010, a technology assessment 25 on KRAS testing in advanced CRC was released by the Ontario Medical Advisory Secretariat, Ministry of Health and Long-Term Care, which was used by the Ontario Health Technology Assessment Advisory Committee to issue a concurrent recommendation. 26 The Kaiser Permanente Center for Health Research has conducted a systematic review of pharmacogenetic testing to predict the value of testing for markers downstream from KRAS (BRAF, NRAS, and PIK3CA mutations, and loss of PTEN and AKT protein expression) toward informing anti-EGFR antibody therapy in mCRC.…”

Section: Background and Clinical Context For The Recommendationmentioning

confidence: 99%

“…Among the findings of this report was that existing evidence was "…sufficient to conclude that patients with mutated KRAS tumors in the setting of metastatic colorectal cancer do not respond to anti-EGFR monoclonal antibody therapy, do not derive overall survival benefit, and may experience decreased progression-free survival. " 11 The summary report from Dahabreh et al 24 details more recent "evidence that KRAS [sic] mutations are predictive of survival, disease progression, and treatment failure in patients with advanced colorectal cancer treated with anti-EGFR antibodies. "…”

Section: Clinical Validitymentioning

confidence: 99%

“…However, there was considerable between-study heterogeneity (P = 0.003 and I 2 = 57%). 24 The Medical Advisory Secretariat 2010 technology assessment 25 conducted a pooled analysis on five of seven studies reporting mean overall survival and progression-free survival among patients undergoing combination therapy with cetuximab and irinotecan. The authors found improved outcomes for patients with wild-type versus mutant KRAS tumors for both overall survival (mean difference of 4.11 months (95% CI 2.62-5.60)) and progression-free survival (mean difference of 3.32 months (95% CI 1.78-4.86)).…”

Section: Clinical Validitymentioning

confidence: 99%

“…As mentioned in the Clinical Validity section, the 2009 BCBS TEC assessment found that by identifying patients with mCRC who will not respond to (and should not receive) anti-EGFR therapy, KRAS testing can prevent both ineffective treatment and treatment-associated toxicity and minimize delay in identifying and administering potentially effective alternative therapies. 11 More recently, in the summary report from Dahabreh et al, 24 a bivariate meta-analysis was conducted for KRAS mutation-based prediction of lack of treatment response (a secondary outcome) with cetuximab or panitumumab, as judged by imaging. The analysis included 841 patients with KRAS mutations, among a total of 2,242 independent patients across 22 studies.…”

Section: Clinical Validity Conclusionmentioning

confidence: 99%

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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?

2013

Genetics in Medicine

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EGAPP REcommEndAtion stAtEmEnt summary of recommendations: 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.Rationale: It has been suggested that patients with 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. Analytic validity:Although no research syntheses that have formally evaluated analytic validity of these tests were found, the EWG was able to draw the following conclusions from assessments included in the evidence reviews under consideration. There is adequate evidence that KRAS mutation analysis reliably and accurately detects common mutations (codons 12 and 13), whereas evidence was inadequate for less frequent KRAS mutations (e.g., codon 61). There is also adequate evidence that testing for BRAF V600E accurately and reliably detects the mutation. For common mutations in NRAS, PIK3CA, and expression of PTEN AKT, there is adequate evidence of accurate and reliable detection. However, much less data exist in support. Furthermore, in the specific context of mCRC, no evidence was found on the analytic validity of immunohistochemistry (IHC) assays for PTEN or AKT expression.clinical val...

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Section: Methodsmentioning

confidence: 99%

Section: Background and Clinical Context For The Recommendationmentioning

confidence: 99%

Section: Clinical Validitymentioning

confidence: 99%

Section: Clinical Validitymentioning

confidence: 99%

Section: Clinical Validity Conclusionmentioning

confidence: 99%

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