BRAF Mutations as Predictive Biomarker for Response to Anti‐EGFR Monoclonal Antibodies. (2nd June 2017)

• Record Type: Journal Article
• Authors: van Brummelen, Emilie M. J.; de Boer, Anthonius; Beijnen, Jos H.; Schellens, Jan H. M.
• Is Part Of: Oncologist. Volume 22:Number 7(2017)
• Page Start: 864
• Page End: 872
• Publication Date: 2017-06-02
• Subjects: BRAF -- RAS -- Cetuximab -- Panitumumab -- Predictive biomarker -- Anti‐epidermal growth factor receptor; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2017-0031
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : 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 ( RAS ) mutations. In addition to the previously established biomarker Kirsten rat sarcoma viral oncogene homolog ( KRAS ) exon 2, cumulative evidence also shows that patients whose tumors harbor KRAS 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 RAS mutated (mt) tumors, treatment response in BRAF mt tumors may also be altered given their important role in the EGFR signaling pathway. However, BRAF is not recommended as predictive biomarker yet because the evidence for the impact of BRAF mutations on treatment outcome is considered insufficient. This article summarizes the evidence for the impact of BRAF 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 BRAF 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 BRAF is even higher than for extended RAS as a biomarker. We therefore advise ESMO and ASCO to reconsider BRAF status as a predictive biomarker for response. Abstract : This article summarizes the evidence for the impact of BRAF mutations on treatment outcome of anti‐EGFR monoclonal antibodies. Based on a review of literature, eight meta‐analyses were included in this study, which consistently show that patients with BRAF mutations have a lack of treatment benefit of anti‐EGFR monoclonal antibodies. Considering the quality and quantity of available evidence, current guidelines may be revised.