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Preoperative Avapritinib for Localized PDGFRA-Mutant GIST: Marked Pathologic Response, but Limited Feasibility at
Tannaz Ranjbarian1,2, Mark Antkowiak1,2, Shirley Sarno1,2
1Division of Surgical Oncology, Department of Surgery, University of California San Diego, San Diego, California, USA.
Background:
Avapritinib 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.
Methods:
We 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.
Results:
All 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.
Conclusions:
In 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.
Insights
Preoperative avapritinib showed significant tumor reduction in localized PDGFRA-mutant GIST, but frequent toxicities limited its use. Further trials are needed to define its role in GIST treatment.
Area of Science:
- Oncology
- Gastrointestinal Oncology
- Precision Medicine
Background:
- Avapritinib is approved for advanced PDGFRA exon 18-mutant GIST.
- Its preoperative use in localized GIST is not well-defined.
Purpose of the Study:
- To evaluate the efficacy and safety of preoperative avapritinib in localized, resectable PDGFRA-mutant GIST.
- To assess radiographic and pathologic responses, treatment duration, adverse events, and surgical outcomes.
Main Methods:
- Retrospective, two-center case series of eight patients.
- Patients received preoperative avapritinib (300 mg daily).
- Evaluated radiographic/pathologic response, AEs, and surgical outcomes.
Main Results:
- Tumor size decreased in 88% of patients (median 25% reduction).
- 50% experienced Grade ≥3 AEs; dose reductions were needed in 38%.
- 5 patients underwent resection with complete or near-complete pathologic response.
Conclusions:
- Preoperative avapritinib demonstrated pathologic activity in localized PDGFRA-mutant GIST.
- Frequent early toxicity at the standard dose limited surgical access for some.
- Routine preoperative use is not recommended; consider for trials or selected patients.
