Mutations as Predictive Biomarker for Response to Anti-EGFR Monoclonal Antibodies.

UNLABELLED

Recently, the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) recommended that patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer could be treated with anti-EGFR monoclonal antibodies (mAbs) cetuximab and panitumumab only in absence of Rat-Sarcoma () mutations. In addition to the previously established biomarker Kirsten rat sarcoma viral oncogene homolog () exon 2, cumulative evidence also shows that patients whose tumors harbor exons 3 or 4 and neuroblastoma rat-sarcoma viral oncogene homolog (NRAS) exons 2, 3, and 4 mutations are found unlikely to benefit from anti-EGFR treatment.In line with the resistance of mutated (mt) tumors, treatment response in mt tumors may also be altered given their important role in the EGFR signaling pathway. However, is not recommended as predictive biomarker yet because the evidence for the impact of mutations on treatment outcome is considered insufficient.This article summarizes the evidence for the impact of mutations on treatment outcome of anti-EGFR mAbs. Based on a review of literature, eight meta-analyses were included that consistently show that patients with mutations have a lack of treatment benefit of anti-EGFR mAbs. After discussing the quality and quantity of available evidence, we conclude that evidence is stronger than suggested by ESMO and ASCO. Additionally, we highlight that the quality of evidence for is even higher than for extended as a biomarker. We therefore advise ESMO and ASCO to reconsider status as a predictive biomarker for response.

IMPLICATIONS FOR PRACTICE

In metastatic colorectal cancer (mCRC), therapy with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab and panitumumab is indicated in absence of mutations. Cumulative evidence shows that patients with mutations, who comprise 10% of the mCRC population, do not benefit from anti-EGFR-antibody treatment. Although guidelines state that evidence for as a predictive marker is insufficient, we highlight that the quality and quantity of evidence is higher than suggested. We therefore encourage the use of as a predictive marker in order to exclude patients from therapy for whom limited treatment benefit is expected.