Avapritinib in the treatment of gastrointestinal stromal tumors (GIST)

Avapritinib is a highly selective inhibitor of mutated KIT and PDGFRA kinases, approved in 2020 for the treatment of patients with gastrointestinal stromal tumors (GIST). It has particular activity against GIST with the PDGFRA D842V mutation associated with imatinib resistance. The safety and efficacy of avapritinib have been evaluated in two clinical trials, NAVIGATOR and VOYAGER, which showed particularly favorable results in patients with the PDGFRA D842V mutation. In the NAVIGATOR study, the objective response rate (ORR) in patients with the mutation was 91%. In the VOYAGER study, the ORR was 17.1% in all patients receiving avapritinib and 42.9% in the group of patients with the PDGFRA D842V mutation. While the efficacy in the subgroup of patients with the mutation was significantly superior to regorafenib, this benefit was not demonstrated for the overall population. In both studies, adverse events were reported in more than 90% of patients, with more than 50% of patients experiencing Grade 3 or higher reactions. The most commonly reported treatment-related adverse events were nausea, fatigue, ane-mia, diarrhea, periorbital edema, and cognitive impairment. Based on the preliminary study results, avapritinib was approved in the United States and the European Union for treating patients with metastatic or unresectable GIST with the PDGRA D842V mutation. It is the first inhibitor showing activity against this mutation. In this review, we summarize the current data on the efficacy and safety of avapritinib and present its place in the diagnostic and therapeutic guidelines.