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Extended RAS Mutation Testing in Metastatic Colorectal Cancer to Predict Response to Anti-EGFR Antibody Therapy

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Key Points

  • Before treatment with anti-EGFR antibody therapy, patients with metastatic colorectal cancer should be tested for mutations in KRAS exons 2, 3, and 4 and NRAS exons 2, 3, and 4.
  • Patients with these mutations are unlikely to benefit from anti-EGFR antibody therapy.

As reported in the Journal of Clinical Oncology by Allegra et al, ASCO has issued a provisional clinical opinion (PCO) update on extended RAS mutation testing in metastatic colorectal cancer to predict response to anti-EGFR monoclonal antibody treatment.

The update revises a 2009 PCO and is based on review by a PCO update committee of 11 systematic reviews with meta-analyses, 2 retrospective analyses, and 2 health technology assessments, in addition to the evidence reviewed in the original PCO. The RAS PCO update committee was co-chaired Carmen J. Allegra, MD, of University of Florida, Gainesville, and Richard L. Schilsky, MD, of ASCO.

Recommendation

The prior PCO recommended testing for mutations in KRAS exon 2 (codons 12 and 13) before treatment with anti-EGFR antibody therapy. The updated PCO recommends that patients considered for anti-EGFR antibody therapy (currently, cetuximab [Erbitux] and panitumumab [Vectibix]) also be tested for mutations in KRAS exons 3 (codons 59 and 61) and 4 (codons 117 and 146) and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) using a Clinical Laboratory Improvement Amendments–certified laboratory. Patients with these mutations are unlikely to benefit from anti-EGFR antibody therapy.

As stated by the panel: “The weight of current evidence indicates that anti-EGFR [monoclonal antibody] therapy should only be considered for treatment of patients whose tumor is determined to not have [these] mutations detected after such extended RAS testing.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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