On June 16, the U.S. Food and Drug Administration (FDA) approved the tyrosine kinase inhibitor avapritinib (Ayvakit) for adult patients with advanced systemic mastocytosis, including patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia.
EXPLORER and PATHFINDER
Efficacy was evaluated in EXPLORER (ClinicalTrials.gov identifier: NCT02561988) and PATHFINDER (ClinicalTrials.gov identifier: NCT03580655), two multicenter, single-arm, open-label clinical trials enrolling patients with advanced systemic mastocytosis. The main efficacy outcome measure was overall response rate per modified IWG-MRT-ECNM criteria, as adjudicated by a central committee. Additional efficacy measures were duration of response, time to response, and changes in individual measures of mast cell burden. Fifty-three patients received daily doses of avapritinib, up to 200 mg.
The overall response rate in all evaluable patients in both trials combined was 57% (95% confidence interval [CI] = 42%–70%) (n = 53), with 28% complete remissions and 28% partial remissions. The median duration of response was 38.3 months (95% CI = 19–not estimable), and the median time to response was 2.1 months.
The most common adverse reactions (incidence ≥ 20%) in patients with advanced systemic mastocytosis were edema, diarrhea, nausea, and fatigue/asthenia.
Avapritinib is not recommended for the treatment of patients with advanced systemic mastocytosis with platelet counts of less than 50 × 109/L.
The recommended avapritinib dose is 200 mg orally once daily for patients with advanced systemic mastocytosis.