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=

MET 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 MET 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 KRAS, NRAS, and BRAF 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 MET amplification, molecular profiling of cell-free DNA (cfDNA) revealed MET 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 MET amplification in cfDNA may be a biomarker of response. A clinical trial targeting MET amplified metastatic CRC is currently underway.