- 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.
- 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.