FDA Approves Avapritinib for the Treatment of PDGFRA-Mutated Gastrointestinal Stromal Tumor

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On January 9, the U.S. Food and Drug Administration (FDA) approved avapritinib (Ayvakit) for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) that harbors platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation. This approval includes GIST that harbors a PDGFRA D842V mutation, which is the most common exon 18 mutation. Avapritinib is an investigational, oral precision therapy that selectively inhibits KIT- and PDGFRA-mutant kinases.

“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST. However, today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Clinical trials showed a high response rate with almost 85% of patients experiencing tumor shrinkage with this targeted drug.”


The FDA approved avapritinib based on the results of the phase I NAVIGATOR trial involving 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with PDGFRA D842V mutation. Patients received avapritinib at 300 mg or 400 mg orally once daily until disease progression or they experienced unacceptable toxicity. The recommended dose was determined to be 300 mg once daily. The trial measured how many patients experienced complete or partial shrinkage (by a certain amount) of their tumors during treatment (overall response rate).

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 mutations, the overall response rate was 89%, with 8% having a complete response and 82% having a partial response. While the median duration of response was not reached, 61% of the responding patients with exon 18 mutations had a response lasting 6 months or longer (31% of patients with an ongoing response were followed for less than 6 months).

Side Effects

Common side effects for patients taking avapritinib were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness. Avapritinib can cause intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued. Avapritinib 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, avapritinib should be withheld and then resumed at the same or reduced dose upon improvement or permanently discontinued.

Health-care professionals should advise pregnant women that avapritinib may cause harm to a developing fetus or newborn baby. Additionally, the FDA advises health-care professionals to tell females of reproductive potential, and males with female partners of reproductive potential, to use effective contraception during treatment with avapritinib and for 6 weeks after the final dose.

The FDA granted this application Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Avapritinib was also granted Fast Track designation and Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. 

The FDA granted approval of avapritinib to Blueprint Medicines Corporation.