TY - JOUR
T1 - Regorafenib for treatment of advanced gastrointestinal stromal Tumors
AU - Overton, Lindsay C.
AU - Heinrich, Michael C.
N1 - Funding Information:
M Heinrich: Consultant --Ariad, Molecular MD, Novartis, Pfizer. Speaker’s honorarium --Onyx, Novartis. Equity interest --Molecular MD. Intellectual property --patent on treatment of GIST with imatinib --assigned to my institution and licensed to Novartis. L Overton has no conflicts of interest. This paper has been supported by a VA Merit Review Grant, GIST Cancer Research Fund, Life Raft Group.
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - Gastrointestinal stromal tumor
KW - KIT
KW - Kinase inhibitors
KW - Platelet-derived growth factor receptor α
KW - Sarcoma
KW - Vascular endothelial growth factor receptor
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U2 - 10.1517/14656566.2014.877888
DO - 10.1517/14656566.2014.877888
M3 - Article
C2 - 24405315
AN - SCOPUS:84893652175
SN - 1465-6566
VL - 15
SP - 549
EP - 558
JO - Expert Opinion on Pharmacotherapy
JF - Expert Opinion on Pharmacotherapy
IS - 4
ER -