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

// Krittiya Korphaisarn 1,2 , Jonathan M. Loree 1 , Van Nguyen 3 , Ryanne Coulson 1 , Vijaykumar Holla 4 , Beate C. Litzenburger 4 , Ken Chen 4 , Gordon B. Mills 4 , Dipen M. Maru 5 , Funda Meric-Bernstan 4 , Kenna R. Mills Shaw 4 and Scott Kopetz 1 1 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2 Department of Medicine, Division of Medical Oncology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand 3 Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 4 Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (IPCT), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 5 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence to: Scott Kopetz, email: // Keywords : metastatic colorectal cancer, regorafenib, survival, biomarker, response Received : March 29, 2017 Accepted : May 20, 2017 Published : June 03, 2017 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.