TY - JOUR
T1 - Regorafenib for treatment of imatinib- and sunitinib-resistant metastatic gastrointestinal stromal tumors
AU - Daughety, Molly M.
AU - Heinrich, Michael C.
N1 - Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2016/6/2
Y1 - 2016/6/2
N2 - Introduction: The treatment of gastrointestinal stromal tumors (GISTs) has been transformed by the use of small molecule KIT/PDGFRA tyrosine kinase inhibitors (TKIs). Unfortunately, most GIST tumors develop resistance to front-line (imatinib) and second-line (sunitinib) therapy. Regorafenib, a multi-targeted KIT/PDGFRA/VEGFR oral TKI, has been shown to improve progression-free survival in the third- or fourth-line setting. Areas covered: This review encompasses the pre-clinical and clinical studies of regorafenib for treatment of GIST. The reviewed studies were all those retrievable using the PubMed database as of December 2015. Expert opinion: Based on the results of a randomized, double-blind, placebo-controlled, phase III study, regorafenib is now firmly established as the only proven third-line therapy. Regorafenib’s activity in this setting is believed to be due to its activity against oncogenic forms of KIT/PDGFRA. Side effects are common with this agent; however, they can be effectively managed with a combination of supportive care, dose interruptions and dose reductions. In frail patients, starting at a lower dose with subsequent dose escalation/de-escalation may improve tolerance and optimize treatment. Regorafenib’s toxicity profile is similar to other oral TKIs with anti-VEGFR activity. Regorafenib is primarily metabolized by CYP3A4, and concomitant use of strong inducers/inhibitors of this enzyme should be avoided.
AB - Introduction: The treatment of gastrointestinal stromal tumors (GISTs) has been transformed by the use of small molecule KIT/PDGFRA tyrosine kinase inhibitors (TKIs). Unfortunately, most GIST tumors develop resistance to front-line (imatinib) and second-line (sunitinib) therapy. Regorafenib, a multi-targeted KIT/PDGFRA/VEGFR oral TKI, has been shown to improve progression-free survival in the third- or fourth-line setting. Areas covered: This review encompasses the pre-clinical and clinical studies of regorafenib for treatment of GIST. The reviewed studies were all those retrievable using the PubMed database as of December 2015. Expert opinion: Based on the results of a randomized, double-blind, placebo-controlled, phase III study, regorafenib is now firmly established as the only proven third-line therapy. Regorafenib’s activity in this setting is believed to be due to its activity against oncogenic forms of KIT/PDGFRA. Side effects are common with this agent; however, they can be effectively managed with a combination of supportive care, dose interruptions and dose reductions. In frail patients, starting at a lower dose with subsequent dose escalation/de-escalation may improve tolerance and optimize treatment. Regorafenib’s toxicity profile is similar to other oral TKIs with anti-VEGFR activity. Regorafenib is primarily metabolized by CYP3A4, and concomitant use of strong inducers/inhibitors of this enzyme should be avoided.
KW - GI stromal tumor
KW - KIT
KW - PDGFRA
KW - Sarcoma
KW - VEGFR
KW - tyrosine kinase inhibitors
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U2 - 10.1080/21678707.2016.1182906
DO - 10.1080/21678707.2016.1182906
M3 - Review article
AN - SCOPUS:84966708024
SN - 2167-8707
VL - 4
SP - 659
EP - 670
JO - Expert Opinion on Orphan Drugs
JF - Expert Opinion on Orphan Drugs
IS - 6
ER -