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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Jia, J; Morse, MA; Nagy, RJ; Lanman, RB; Strickler, JH

Published Date

  • 2018

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 305 -

PubMed ID

  • 30211110

Pubmed Central ID

  • PMC6121109

International Standard Serial Number (ISSN)

  • 2234-943X

Digital Object Identifier (DOI)

  • 10.3389/fonc.2018.00305


  • eng

Conference Location

  • Switzerland