Avapritinib in unresectable or metastatic gastrointestinal stromal tumor with PDGFRA exon 18 mutation: safety and efficacy

Introduction Avapritinib (formerly known as BLU-285) is an orally available type I tyrosine kinase inhibitor that, in 2020, obtained regulatory approval for the treatment of patients with gastrointestinal stromal tumors (GISTs) harboring a primary mutation in PDGFRA exon 18, including the PDGFRA D842V mutation. Areas covered Herein, we comprehensively review the available efficacy and safety data on avapritinib, with the final goal of providing practical knowledge to both sarcoma and community-based oncologists for the correct management of this rare GIST subpopulation with this novel therapy. Expert opinion The approval of avapritinib in GIST is a milestone in precision oncology, as this is the first agent ever demonstrating unequivocal antitumoral activity in GIST driven by the multi-resistant PDGFRA D842V mutation. The safety profile is manageable and tolerability-guided dose adjustment is recommended to manage treatment-related adverse events without compromising efficacy. Based on its unprecedented activity, avapritinib should be considered as first-line therapy for GIST patients harboring this mutation. We strongly recommend to determine KIT/PDGFRA genotype in order to identify the different GIST molecular subtypes and guide treatment decision.