Evaluation of the effectiveness and safety of avapritinib in real-world Spanish cases with gastrointestinal stromal tumor and D842V-PDGFRA mutation

Abstract

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common sarcoma subtype. Patients with unresectable or metastatic GISTs harboring the D842V mutation in the PDGFRA gene have a poor prognosis due to intrinsic resistance to imatinib and all other approved tyrosine kinase inhibitors. Avapritinib, targeting this mutation, is the first agent approved for patients with unresectable or metastatic GIST that have the PDGFRA D842V mutation. This study assesses the effectiveness and safety of avapritinib in real-world clinical scenarios involving Spanish patients with this mutation.

Materials and methods: The AVARWE study is a descriptive, retrospective, multicenter observational study of 21 patients treated with avapritinib across 13 Spanish centers from June 9, 2023, to December 18, 2023. Data collected included patient demographics, disease characteristics, treatment history, and response rates based on RECIST criteria. The main outcomes, progression-free survival (PFS) and overall survival (OS), were measured, with safety assessed through adverse events documentation according to CTCAE criteria.

Results: Median PFS 35.6 was months and median OS was 42.2 months, with survival rates at 1, 5, and 3 years demonstrating avapritinib effectiveness. The objective response rate was 76.2% for partial response and 4.8% for complete response. Avapritinib enabled surgical intervention in previously unresectable cases and was generally well-tolerated, with manageable adverse events.

Conclusion: Avapritinib extends PFS and OS among patients with PDGFRA D842V-mutant GIST in real-world practice, mirroring pivotal trial outcomes. Its substantial activity supports its use as a first-line therapy for this subgroup. The manageable safety profile reinforces avapritinib viability for routine use. Given the rarity of these cases, it is advised to consult sarcoma-expert units.

Keywords: PDGFRA; D842V mutation; GIST; avapritinib; gastrointestinal stromal tumor; outcomes; treatment.