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New Drug OK'd for GIST With Treatment-Resistant Mutation

— Avapritinib targets difficult-to-treat PDGFRA exon 18 mutation

MedpageToday

WASHINGTON -- The for treating gastrointestinal stromal tumors (GIST) with a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation.

"GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST," Richard Pazdur, MD, the FDA's top oncology official, said in a statement. "However, today's approval provides patients with the first drug specifically approved for GIST harboring this mutation."

GISTs, which typically develop in the stomach and small intestine, involve specialized nerve cells on the walls of the gastrointestinal tract and activating mutations in PDGFRA are attributable to roughly 10% of cases.

Support for avapritinib's approval came from a dose-finding trial of 43 patients harboring the rare mutation. The overall response rate to avapritinib was 84%, which included complete responses (CRs) in 7%. In the subgroup of 38 patients with a PDGFRA D842V mutation, 89% responded to treatment, including CRs in 8%.

Median duration of response was not reached, but 61% of the patients had responses that lasted 6 months or beyond -- 31% had ongoing responses but were followed for less than 6 months.

The recommended dose is 300 mg once daily.

Common adverse events in the study included abdominal pain, changes in hair color, constipation, cognitive difficulties and dizziness, decreased appetite, diarrhea, edema, fatigue, increased lacrimation, nausea and vomiting, and rash.

In its approval notice, FDA called for dose reductions or treatment cessation if intracranial hemorrhage occurs and for dose interruptions or cessation if severe central nervous system effects develop (i.e., cognitive impairment, dizziness, hallucinations, or sleep, mood, or speech disorders).

The agency also warned against use in pregnant women and recommended contraceptive use for men or women taking avapritinib treatment until 6 weeks following the last dose.