Genomic analysis of exceptional responder to regorafenib in treatment-refractory metastatic rectal cancer: A case report and review of the literature

Krittiya Korphaisarn, Jonathan M. Loree, Van Nguyen, Ryanne Coulson, Vijaykumar Holla, Beate C. Litzenburger, Ken Chen, Gordon B. Mills, Dipen M. Maru, Funda Meric-Bernstan, Kenna R.Mills Shaw, Scott Kopetz

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

We present the case of a 53-year-old male with metastatic rectal cancer who was treatment resistant to FOLFOX and FOLFOXIRI. Due to a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, regorafenib was given in the third line setting. Surprisingly, the patient had a prolonged partial response that lasted 27 months. Mutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for this unusual event. A poorly characterized but nontransforming mutation in Fms-like tyrosine kinase 4 (FLT4) was present in the tumor. Prior to and at the time of clinical progression, we found amplification of fibroblast growth factor receptor 1 (FGFR1) and epidermal growth factor receptor (EGFR), loss of the FLT4 mutation, and gain of KIT proto-oncogene receptor tyrosine kinase (KIT) G961S suggesting potential roles in acquired resistance.

Original languageEnglish (US)
Pages (from-to)57882-57888
Number of pages7
JournalOncotarget
Volume8
Issue number34
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • Biomarker
  • Metastatic colorectal cancer
  • Regorafenib
  • Response
  • Survival

ASJC Scopus subject areas

  • Oncology

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