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COLORECTAL CANCER: The FDA have approved the kinase inhibitor avapritinib for patients with metastatic gastrointestinal stromal tumour (GIST) harbouring a PDGFRA exon 18 mutation


Jan. 20, 2020



FDA January 9, 2020:


On January 9, 2020, the Food and Drug Administration approved avapritinib (AYVAKITTM, Blueprint Medicines Corporation) for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including D842V mutations.

Avapritinib is the first therapy approved for patients with GIST harboring a PDGFRA exon 18 mutation.

Efficacy was investigated in NAVIGATOR (NCT02508532), a multi-center, single-arm, open-label trial enrolling 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with PDGFRA D842V mutations. The trial initially enrolled patients at a starting dose of 400 mg orally once daily, which was later reduced to the recommended dose of 300 mg orally once daily due to toxicity. Patients received avapritinib until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate (ORR) based on disease assessment by independent radiological review using modified RECIST 1.1 criteria. An additional efficacy outcome measure was response duration.

For patients harboring a PDGFRA exon 18 mutation, the ORR was 84% (95% CI: 69%, 93%), with 7% complete responses and 77% partial responses. For the subgroup of patients with PDGFRA D842V mutations, the ORR was 89% (95% CI: 75%, 97%), with 8% complete responses and 82% partial responses. The median response duration was not reached with a median duration of follow-up for all patients of 10.6 months (range 0.3 to 24.9 months); 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).

The most common adverse reactions (incidence ≥ 20%) in patients who received avapritinib were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash and dizziness.

The recommended avapritinib dose is 300 mg orally once daily on an empty stomach, at least one hour before and two hours after a meal.