AUTHOR=Jia Jingquan , Morse Michael A. , Nagy Rebecca J. , Lanman Richard B. , Strickler John H. 

TITLE=Cell-Free DNA Profiling to Discover Mechanisms of Exceptional Response to Cabozantinib Plus Panitumumab in a Patient With Treatment Refractory Metastatic Colorectal Cancer

JOURNAL=Frontiers in Oncology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00305

DOI=10.3389/fonc.2018.00305

ISSN=2234-943X

ABSTRACT=<p><italic>MET</italic> amplification is rare in treatment-naïve metastatic colorectal cancer (CRC) tumors, but can emerge as a mechanism of resistance to anti-EGFR therapies. Preclinical and clinical data suggest that patients with <italic>MET</italic> amplified tumors benefit from MET-targeted therapy. Cabozantinib is an inhibitor of multiple tyrosine kinases, included c-MET. Panitumumab is an inhibitor of EGFR. This report describes a patient with <italic>KRAS, NRAS</italic>, and <italic>BRAF</italic> wild-type metastatic CRC who experienced disease progression on all standard chemotherapy and anti-EGFR antibody therapy. The patient was enrolled in a clinical trial evaluating the combination of cabozantinib plus panitumumab. After only 6 weeks of treatment, the patient experienced a significant anti-tumor response. Although tumor tissue was negative for <italic>MET</italic> amplification, molecular profiling of cell-free DNA (cfDNA) revealed <italic>MET</italic> amplification. This case represents the first report showing the activity of cabozantinib in combination with panitumumab in a patient with metastatic CRC, and suggests that <italic>MET</italic> amplification in cfDNA may be a biomarker of response. A clinical trial targeting <italic>MET</italic> amplified metastatic CRC is currently underway.</p>