(P 179) NEOADJUVANT AVAPRITINIB IN PDGFRA-MUTANT GIST: NEAR COMPLETE PATHOLOGICAL RESPONSES AT THE COST OF HIGH ADVERSE EVENT RATES

Objective: To evaluate the therapeutic response and safety profile of neoadjuvant avapritinib in patients with localized PDGFRA-mutant gastrointestinal stromal tumors (GIST).

Methods: A retrospective analysis was performed on six patients with biopsy-confirmed, localized PDGFRA-mutant gastric GIST treated with neoadjuvant avapritinib (300 mg daily) between 2020 and 2025. Tumor response was assessed by change in maximal tumor diameter between baseline and post-treatment CT scans according to radiology reports and independent review. In patients who underwent resection, surgical specimens were evaluated by board-certified pathologists for tumor viability, necrosis, and mitotic index in accordance with institutional protocols. Adverse events were graded according to CTCAE version 5.0.

Results: The median duration of avapritinib therapy was 2 months (range, < 1 to 6 months). Among all six patients, radiographic tumor shrinkage ranged from 2% to 49%, with greater regression associated with longer treatment duration. Three patients discontinued therapy early; all experienced grade ≥3 treatment-related adverse events, including one fatal intracranial hemorrhage. Of the three who underwent surgical resection with curative intent, complete (100%) or near-complete (98%) pathologic responses were achieved, highlighting discordance between radiographic and pathologic response in avapritib-treated tumors.

Conclusion: Neoadjuvant avapritinib induced tumor regression in PDGFRA-mutant GIST; however, the high incidence of serious treatment-related toxicities, including a fatal adverse event, raises concern regarding its tolerability and real-world applications. These findings emphasize the necessity of cautious clinical consideration, with close attention to patient selection, risk-benefit balance, and alternative therapeutic approaches when prescribing avapritinib in the neoadjuvant setting.