Avapritinib (KIT D816V) Beats Midostaurin/Cladribine on OS in AdvSM

Avapritinib, a selective KIT D816V inhibitor, was compared via IPTW-adjusted external controls to midostaurin (multikinase/KIT) or cladribine (purine analog) using EXPLORER/PATHFINDER trial patients (n=176) versus real-world midostaurin (n=99) or cladribine (n=49). Median OS was not reached for avapritinib (95% CI 46.9 mo–NE) vs 28.6 mo (midostaurin) and 23.4 mo (cladribine); OS favored avapritinib (HR 0.59 vs midostaurin; 0.32 vs cladribine), with longer treatment duration (HR 0.63; 0.14) and greater tryptase reductions (−72.8% vs midostaurin; −25.0% vs cladribine); these patterns held in 1L and 2L+ subsets. Against prospective benchmarks—midostaurin ORR ~60% with ~58% median tryptase drop and avapritinib’s pivotal high clinical/molecular responses—the survival advantage is compelling but nonrandomized and short on on-study safety details.