Reference Detail

Ref Type

Journal Article

PMID

(27004155)

Authors

Loaiza-Bonilla A, Jensen CE, Shroff S, Furth E, Bonilla-Reyes PA, Deik AF, Morrissette J

Title

KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cureus	8	2	2016 Feb 03	e478	Cureus

URL

Abstract Text

This is the case of an 84-year-old woman diagnosed with Stage IVb colon adenocarcinoma (CRC) metastatic to the liver, retroperitoneum, anastomotic site, and distal rectal sigmoid colon. She experienced intolerable side effects to systemic chemotherapy with 5-fluorouracil and bevacizumab, as well as disease progression. Next generation sequencing of her tumor was ordered, and further discussion of her malignancy's genomic information took place at a multidisciplinary molecular tumor board. The patient had mutations in KRAS (Kirsten rat sarcoma viral oncogene homolog) which made her ineligible for epidermal growth factor receptor (EGFR) inhibitors; however, a KDR p.R961W c.2881C>T mutation was noted as a variant of unknown significance (VUS). KDR (kinase insert domain receptor) is the human gene encoding for vascular endothelial growth factor receptor 2 (VEGFR-2). She was then considered a suitable candidate for regorafenib, which she could only tolerate at a low dose of 40 mg daily, with the intent of prolonging her survival and to optimize her quality of life. We report her excellent tolerance and exceptional response to low dose regorafenib, including symptomatic, tumor marker, and sustained partial metabolic radiological improvement. In the largest Phase III trial of regorafenib in CRC, only five patients (1%) of 760 experienced a partial response (versus one patient, 0.4%, receiving placebo). KDR R961W mutation has been described but no functional data has been reported. This mutation occurs in the tyrosine kinase domain of the VEGFR-2. Regorafenib targets VEGFR-2 (KDR). Hereby we hypothesize KDR mutation as a novel predictive biomarker to exceptional response to regorafenib in metastatic colorectal cancer. To our knowledge, this is the first reported case of the potential correlation between KDR mutation and regorafenib use for the successful management of a patient with advanced CRC, leading to what is considered an exceptional response. Further studies based on this preliminary data are warranted.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References