Observational studyCancer medicine2026
Preoperative Avapritinib for Localized PDGFRA-Mutant GIST: Marked Pathologic Response, but Limited Feasibility at Standard Dosing.
Observational study in Cancer medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
backgroundAvapritinib is a selective tyrosine kinase inhibitor approved for advanced PDGFRA exon 18-mutant gastrointestinal stromal tumors (GIST), including the imatinib-resistant D842V variant. However, its role in the preoperative setting for localized, resectable disease has not been defined.
methodsWe conducted a retrospective two-center exploratory case series of eight patients with localized, resectable PDGFRA-mutant gastric GIST who received preoperative avapritinib between 2020 and 2025. Radiographic and pathologic responses, treatment duration, adverse events (AEs), and surgical outcomes were evaluated.
resultsAll patients initiated avapritinib at 300 mg daily. Median treatment duration was 2 months (range, < 1-21 months). Tumor size decreased in seven patients (88%), with a median reduction of 25% and an overall range from -51% to +29%. Three patients (38%) met RECIST-based thresholds for partial response (≥ 30% reduction). Five patients underwent surgical resection, all achieving complete (0% viable tumor) or near-complete (≤ 5% viable tumor) pathologic response. Dose reductions were required in three patients due to toxicity; however, tumor regression continued in all. Treatment-related grade ≥ 3 AEs occurred in 50% of patients, including one fatal intracranial hemorrhage. Most toxicities emerged within two months, and most nonfatal toxicities improved with dose adjustment or discontinuation.
conclusionsIn this exploratory two-center case series, preoperative avapritinib demonstrated marked pathologic activity in localized PDGFRA-mutant GIST, including after dose reduction in some patients. However, early toxicity at the standard 300 mg dose was frequent and, in several cases, prevented patients from reaching planned surgery. These findings argue against routine preoperative avapritinib use and support limiting this approach to clinical trials or highly selected patients with a compelling surgical rationale until prospective data are available.
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