Regorafenib for treatment of advanced gastrointestinal stromal Tumors

Lindsay C. Overton, Michael C. Heinrich

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Introduction: Gastrointestinal stromal tumors (GISTs) are abdominal sarcomas which are extremely refractory to chemotherapy treatment. The treatment of GISTs has been revolutionized by use of KIT/platelet-derived growth factor receptor-α (PDGFRA) kinase inhibitors. Unfortunately, most tumors develop resistance to front-line (imatinib) or second-line (sunitinib) therapy. Regorafenib, a KIT/PDGFRA/vascular endothelial growth factor receptor (VEGFR) oral kinase inhibitor, has been shown to improve progression-free survival in the third- or fourth-line setting. Areas covered: This review covers the preclinical and clinical studies of regorafenib for treatment of GIST. A literature search on regorafenib was carried out using the PubMed database up to October 2013. Expert opinion: Currently, imatinib and sunitinib represent the only proven first- and second-line therapies, respectively, for advanced GISTs. Based on the results of a Phase III study, regorafenib is now established as the only proven third-line therapy. Regorafenib activity in this setting is believed to be due to its activity against oncogenic forms of KIT/PDGFRA. Although side effects are common with this agent, they can be effectively managed with a combination of supportive care, dose interruptions/reductions. The toxicity profile is similar to other oral kinase inhibitors with anti-VEGFR activity. Regorafenib is mainly metabolized by CYP3A4, and concomitant use of strong inducers/inhibitors of this enzyme should be avoided.

Original languageEnglish (US)
Pages (from-to)549-558
Number of pages10
JournalExpert Opinion on Pharmacotherapy
Issue number4
StatePublished - Mar 2014


  • Gastrointestinal stromal tumor
  • KIT
  • Kinase inhibitors
  • Platelet-derived growth factor receptor α
  • Sarcoma
  • Vascular endothelial growth factor receptor

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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