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RAS amplification as a negative predictor of benefit from Anti-EGFR-containing therapy regimens in metastatic colorectal cancer

Published

June 2021

Citation

Schrock AB, Lee JK, Sandhu J, Madison R, Cho-Phan C, Snider JW, Castellanos E, Venstrom JM, Fakih M. RAS Amplification as a Negative Predictor of Benefit from Anti-EGFR-Containing Therapy Regimens in Metastatic Colorectal Cancer. Oncologist. 2021 Jun;26(6):469-475. https://pubmed.ncbi.nlm.nih.gov/33465286/

Our summary

RAS short variant mutations in colorectal cancer are associated with a lack of benefit from growth factor receptor (EGFR) monoclonal antibody (EGFRmAb). Yet, clinical implications for RAS amplification as a biomarker for anti-EGFR are unknown. This study found that patients with RAS amplification without RAS mutations have poor outcomes on EGFRmAb.

Why this matters

The increasing sophistication of genomic testing tools continues to deepen our understanding of drivers of responsiveness or resistance to treatment. This work represents a prime example of that progress. Mutations on RAS genes have been known to drive resistance to EGFRmAbs, but, until now, little was known about the impact of other RAS alterations that are far more rare and would not be detected by the most widely used mutation tests. This clinicogenomic RWD study unlocked the potential to learn about those patients and their outcomes, expanding the reach of precision oncology.

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