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

Frontiers in Oncology

John H. Strickler¹  Jingquan Jia¹  Michael A. Morse¹  Richard B. Lanman²  Rebecca J. Nagy² 

[1] Department of Medicine, Duke University Medical Center, Durham, NC, United States;Guardant Health, Inc., Redwood City, CA, United States;

关键词: MET amplification;    metastatic colorectal cancer;    cabozantinib;    cell-free DNA;    ctDNA;   

DOI  :  10.3389/fonc.2018.00305

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown