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JOURNAL ARTICLE
REVIEW
Gastrointestinal Stromal Tumors: What Is the Best Sequence of TKIs?
In our practice, we evaluate the mutation status of advanced unresectable disease to guide decisions on use of tyrosine kinase inhibitor (TKI) therapy. This review focuses on management of GIST with KIT and PDGFRA mutations. Imatinib is first-line treatment for unresectable gastrointestinal stromal tumors (GISTs) unless they harbor a PDGFRA D842V mutation; it is recommended to escalate imatinib to twice daily dosing for KIT exon 9 mutant tumors. When patients progress on first-line treatment, treatment is changed to sunitinib followed by regorafenib; while the spectrum of activity against resistance mutations varies with these agents, routine biopsies provide data on one area of disease and ctDNA has not been validated prospectively. For those with a PDGFRA D842V mutation, avapritinib is the first TKI to lead to tumor response and disease control. Ripretinib is approved in the 4th line setting, with limited data on its benefit for PDGFRA D842V GIST. Avapritinib can be considered for treatment beyond ripretinib for KIT mutant disease. The efficacy of other TKIs tested in GIST is reviewed. Ongoing therapy provides palliative benefit and should be continued given rapid decline observed off of treatment.
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