First targeted therapy approved to treat patients with GI stromal tumors, rare mutation

A kinase inhibitor was approved to treat adults with an unresectable or metastatic gastrointestinal (GI) stromal tumor who harbor a platelet-derived growth factor receptor alpha exon 18 mutation.


The FDA on Jan. 9 approved the first treatment for patients with gastrointestinal (GI) stromal tumors and a specific genetic mutation.

Avapritinib (Ayvakit), a kinase inhibitor, is now approved to treat adults with an unresectable or metastatic GI stromal tumor who harbor a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation. The approval includes GI stromal tumors that harbor a PDGFRA D842V mutation, the most common exon 18 mutation. GI stromal tumors with the mutation do not respond to standard therapies, the FDA said.

FDA approval was based on the results of a clinical trial of 43 patients with GI stromal tumors harboring a PDGFRA exon 18 mutation, including 38 patients with PDGFRA D842V mutation. Patients received the drug (300 or 400 mg orally once daily) until disease progression or until they experienced unacceptable toxicity. The recommended dose was found to be 300 mg/d.

For patients harboring a PDGFRA exon 18 mutation, the overall response rate was 84%, with 7% having a complete response and 77% having a partial response. For the subgroup of patients with PDGFRA D842V mutation, the overall response rate was 89%, with 8% having a complete response and 82% having a partial response. Sixty-one percent of the responding patients with exon 18 mutation had a response lasting six months or longer.

Common side effects of the drug were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness. It can cause intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued. The drug can also cause central nervous system effects, including cognitive impairment, dizziness, sleep disorders, mood disorders, speech disorders, and hallucinations. If this happens, depending on the severity, the drug should be withheld and then resumed at the same or a reduced dose upon improvement or permanently discontinued, the FDA said.