Avapritinib

Avapritinib is a potent, selective tyrosine kinase inhibitor that targets KIT and PDGFRA kinases, including mutant forms that drive certain cancers. It binds to the active conformation of these kinases to block signaling required for tumor cell growth and survival. It is approved for adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) that harbor a PDGFRA exon 18 mutation, including the D842V substitution. The drug has also been studied in other KIT-mutant diseases, such as systemic mastocytosis, where KIT mutations contribute to disease biology.

In GIST, avapritinib demonstrated activity in patients whose tumors carry PDGFRA exon 18 mutations, leading to regulatory approval in this mutation-defined subgroup. Studies in systemic mastocytosis and other KIT-mutant conditions have explored its efficacy and safety, reflecting its broad kinase-targeting profile. The clinical experience highlights rapid and ongoing tumor responses in eligible patients, with ongoing evaluation of long-term outcomes and resistance mechanisms.

Adverse effects associated with avapritinib are diverse and can be serious. Common events include edema, nausea, diarrhea, vomiting, fatigue, and changes in blood counts such as anemia or thrombocytopenia. More serious risks described in clinical practice and labeling include intracranial hemorrhage and cognitive or mood-related effects; patients require careful monitoring, dose adjustments, and management of electrolytes and comorbid conditions. As with other kinase inhibitors, potential drug interactions exist, particularly with strong inhibitors or inducers of hepatic CYP3A enzymes, which can alter drug exposure.

Avapritinib is marketed under the brand name Ayvakit and was developed by Blueprint Medicines in collaboration with Genentech. It is prescribed in the appropriate mutation-defined contexts and studied in ongoing trials for other KIT/PDGFRA-driven diseases.