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Ayvakit First Targeted Therapy Approved for Gastrointestinal Stromal Tumors with PDGFRA Mutation

February 2020 Vol 13, Special Issue: Payers' Perspectives in Oncology - Drug Updates, FDA Approvals

On January 9, 2020, the FDA accelerated the approval of avapritinib (Ayvakit; Blueprint Medicines Corporation), a kinase inhibitor, for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a 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. The FDA granted breakthrough therapy and orphan drug designations to avapritinib.

“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. “Clinical trials showed a high response rate with almost 85% of patients experiencing tumor shrinkage with this targeted drug.”

The activating mutations in PDGFRA have been linked to the development of GIST, and up to approximately 10% of patients with GIST have this type of gene mutation.

The approval of avapritinib was based on a clinical trial of 43 patients with GIST associated with a PDGFRA exon 18 mutation, including 38 patients with PDGFRA D842V mutation. Patients received avapritinib 300 mg or 400 mg orally once daily until disease progression or until unacceptable toxicity. Based on the study’s results, the recommended dose of avapritinib is 300 mg once daily.

The primary end point was overall response rate (ORR). Among patients with a PDGFRA exon 18 mutation, the ORR was 84%, consisting of 7% complete responses and 77% partial responses. For patients with PDGFRA D842V mutation, the ORR was 89%, including 8% with a complete response and 82% with a partial response.

The median duration of response was not yet reached, but in the 61% of the patients with exon 18 mutations who had a response, the response lasted ≥6 months (31% of patients with an ongoing response were followed for <6 months).

The common side effects with avapritinib were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased tearing (lacrimation), abdominal pain, constipation, rash, and dizziness. Avapritinib can cause intracranial hemorrhage and central nervous system effects, and this drug may cause harm to a fetus.

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Last modified: August 30, 2021