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.