Gastrointestinal Stromal Tumor (GIST): Therapy by Mutation

Gastrointestinal Stromal Tumor (GIST): Therapy by Mutation: overview

This algorithm organizes therapy for gastrointestinal stromal tumor (GIST) by mutation, because genotype determines sensitivity to tyrosine kinase inhibitors.

Tumors with imatinib-sensitive KIT or PDGFRA mutations (that is, not PDGFRA D842V) receive first-line imatinib. PDGFRA D842V-mutant tumors are treated with avapritinib, which is specific for this mutation. SDH-deficient, NTRK, NF1 and BRAF-driven tumors call for genotype-directed therapy, such as a TRK inhibitor for NTRK fusions, or a clinical trial. After complete resection of high-risk disease, adjuvant imatinib is given for at least 3 years on a risk-adapted basis. After progression on imatinib, sunitinib is the second-line option, relevant in the setting of secondary KIT mutations. Regorafenib is the third-line option (GRID), and ripretinib is used in the fourth line (INVICTUS). Mutation testing is therefore the first step, since it identifies both the tumors that will respond to imatinib and those that need a different targeted agent.

Trials behind this algorithm

• Avapritinib/NAVIGATOR trial Heinrich MC et al, Lancet Oncol, 2020; PMID:32615108.
• INVICTUS trial Blay JY et al, Serrano C et al, Lancet Oncol, 2020; PMID:32511981

Background reading: Gastrointestinal stromal tumor (GIST) board review notes.