Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N = 176) and patients treated with best available therapy (BAT; N = 141). A multi-center, observational, retrospective chart review study was conducted at six study sites (four European, two American) to collect data from patients with AdvSM who received BAT; these data were pooled with data from EXPLORER and PATHFINDER. Comparisons between outcomes of OS, duration of treatment (DOT), and maximum reduction in serum tryptase were conducted between the treatment cohorts, with adjustment for key covariates. The results indicated that the avapritinib cohort had significantly better survival (adjusted hazard ratio (HR) (95% confidence interval (CI)): 0.48 (0.29, 0.79); p = 0.004) and significantly longer DOT (HR: 0.36 (0.26, 0.51); p < 0.001) compared to the BAT cohort. Additionally, the mean difference in percentage maximum reduction in serum tryptase levels was 60.3% greater in the avapritinib cohort (95% CI: −72.8, −47.9; p < 0.001). With no randomized controlled trials comparing avapritinib to BAT, these data offer crucial insights into the improved efficacy of avapritinib for the treatment of AdvSM.

晚期系统性肥大细胞增多症 (AdvSM) 是一种罕见的髓系肿瘤，与较差的总生存期 (OS) 相关。本研究 (NCT04695431) 比较了在 1 期 EXPLORER (NCT0256198) 和 2 期 PATHFINDER (NCT03580655) 试验 ( N = 176)中接受 avapritinib 治疗的 AdvSM 患者与 接受最佳可用疗法 (BAT; N ) 治疗的患者之间的临床结果 = 141)。在六个研究地点（四个欧洲，两个美国）进行了一项多中心、观察性、回顾性图表审查研究，以收集接受 BAT 的 AdvSM 患者的数据；这些数据与来自 EXPLORER 和 PATHFINDER 的数据合并。在治疗组之间进行了 OS、治疗持续时间 (DOT) 和血清类胰蛋白酶最大降低的结果之间的比较，并对关键协变量进行了调整。结果表明，avapritinib 队列具有显着更好的生存率（调整后的风险比（HR）（95% 置信区间（CI））：0.48（0.29，0.79）；p  = 0.004）和显着更长的 DOT（HR：0.36（0.26， 0.51); p < 0.001) 与 BAT 队列相比。此外，在 avapritinib 队列中，血清类胰蛋白酶水平最大降低百分比的平均差异为 60.3%（95% CI：-72.8，-47.9；p  < 0.001）。由于没有将 avapritinib 与 BAT 进行比较的随机对照试验，这些数据为提高 avapritinib 治疗 AdvSM 的疗效提供了重要见解。