FDA Grants Approval to Avapritinib for Patients with GIST

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On January 9, 2020, the FDA approved avapritinib (Ayvakit; Blueprint Medicines), a kinase inhibitor, for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutations, including PDGFRA D842V mutations. The FDA designated avapritinib as a breakthrough therapy and an orphan drug. Avapritinib was also granted Fast Track designation, which expedites the review of drugs to treat serious conditions and fill an unmet medical need.

GIST is a type of sarcoma that can start anywhere along the gastrointestinal tract, but most frequently arises in the stomach and the small intestine. Approximately 10% of patients with GIST have PDGFRA mutations; the most common PDGFRA exon 18 mutation is the D842V mutation. Avapritinib is the first targeted therapy approved to treat a genomically defined population of patients with GIST.

This approval was based on combined safety results from multiple clinical trials and efficacy data from the phase 1, multicenter, single-arm, open-label NAVIGATOR clinical trial of 43 patients with GIST harboring PDGFRA exon 18 mutations, including 38 patients with D842V mutations. Data were evaluated by independent reviewers using modified Response Evaluation Criteria in Solid Tumors version 1.1 criteria for GIST.

Patients received avapritinib 300 mg or 400 mg orally once daily until disease progression or unacceptable toxicity. The primary end point was overall response rate (ORR). In patients harboring PDGFRA exon 18 mutations, the ORR was 84% (7% complete response [CR]; 77% partial response [PR]). In the subgroup of patients with PDGFRA D842V mutations, the ORR was 89% (8% CR; 82% PR). Median duration of response was not reached. Of the responding patients, 61% of those with PDGFRA exon 18 mutations had a response lasting ≥6 months (31% of patients with an ongoing response were followed for <6 months).

“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, in an agency press release.

The most common (≥20%) adverse effects associated with avapritinib were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness.

The FDA advises females of reproductive potential and males with female partners of reproductive potential that avapritinib use may impair fertility and cause harm to a developing fetus or newborn baby. Females and males of reproductive potential should use effective contraception during treatment with avapritinib and for 6 weeks after the final dose, and breastfeeding should be avoided for 2 weeks after the final dose.

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Last modified: August 30, 2021
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