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

Year: 2018

Type: article

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.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2018.00305

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

Institutions: Duke Medical Center, Guardant (United States)

Language: English

Topic: Colorectal Cancer Treatments and Studies

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801