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Uptodate Reference Title
Approach to initial therapy for advanced and metastatic gastrointestinal stromal tumors based on tumor mutational status
Approach to initial therapy for advanced and metastatic gastrointestinal stromal tumors based on tumor mutational status
Patients with advanced or metastatic, unresectable GIST are typically treated with systemic targeted therapy as initial treatment. Listed treatments are preferred options, although alternative agents that are not listed may also be effective. Clinical trials are encouraged where available.
PDGFRA: platelet-derived growth factor receptor alpha; GIST: gastrointestinal stromal tumors; SDH: succinate dehydrogenase; TKIs: tyrosine kinase inhibitors; NF1: neurofibromatosis 1. * An assessment of tumor mutational status using DNA sequencing techniques is advised during the initial evaluation of patients with advanced or metastatic disease because clinical responses to imatinib (and other TKIs) correlate with tumor genotype. However, for most patients, systemic treatment with imatinib can be initiated empirically while awaiting confirmation of tumor mutational status. Treatment may be subsequently modified once tumor mutational status becomes available. However, for those with histologies suggestive of imatinib resistance (eg, SDH deficiency or NF1-related disease), referral to a tertiary care center for clinical trials is warranted, rather than empiric imatinib. Refer to UpToDate content on diagnosis and treatment of GIST. ¶ KIT and PDGFRA are mutually exclusive oncogenic mutations in patients with GIST. Δ Patients with tumors that are KIT and PDGFRA wild-type are typically resistant to imatinib and may harbor certain mutations (eg, SDH deficiency, NF1, and BRAF V600E). Refer to UpToDate content on classification of GIST. ◊ Other KIT mutations involving exons 13, 14, 17, or 18 are extremely rare, and the optimal treatment approach varies. Referral for clinical trials at a sarcoma center of excellence is encouraged. § Patients with a KIT exon 9 mutation demonstrate some relative resistance to imatinib, and higher doses of imatinib are preferred. ¥ For patients with a PDGFRA D842V mutation who exhibit asymptomatic and/or indolent disease, a period of observation is preferable to immediate treatment with avapritinib in order to avoid treatment-related toxicities, such as potential cognitive impairment.
