FDA gives nod to avapritinib for mutant GIST

  • US Food and Drug Administration

  • curated by Jim Kling
  • Univadis Clinical Summaries
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Takeaway

  • The US FDA has approved avapritinib for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) involving platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutations, including D842V mutations.

Why this matters

  • The drug is the first therapy approved for GIST with PDGFRA exon 18 mutations.

Key points

  • The approval is based on the NAVIGATOR trial, which was a multicenter, single-arm, open-label study of 43 patients with a PDGFRA exon 18 mutation, including 38 with PDGFRA D842V mutations.
  • The initial dose in the trial was 400 mg orally once daily, but this was reduced to 300 mg because of toxicity.
  • Overall response rate (ORR), 84% (95% CI, 69%-93%).
  • Complete response rate, 7%.
  • Among patients with PDGFRA D842V mutations: 
    • ORR, 89% (95% CI, 75%-97%). 
    • Complete response, 8%.
  • After a median follow-up of 10.6 months, the median response duration was not reached.
  • 61% had a response duration of >6 months. 
  • 31% of those with an ongoing response were followed
  • Adverse reactions affecting 20% or more of patients included edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness.
  • Full prescribing information.