Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis.
Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis.
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DOI：
10.1038/leu.2016.148
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发表时间：
2016-08
期刊：
影响因子：
11.4
通讯作者：
Barbui T
中科院分区：
文献类型：
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作者：
Harrison CN;Vannucchi AM;Kiladjian JJ;Al-Ali HK;Gisslinger H;Knoops L;Cervantes F;Jones MM;Sun K;McQuitty M;Stalbovskaya V;Gopalakrishna P;Barbui T
Ruxolitinib 是一种 Janus 激酶 (JAK) (JAK1/JAK2) 抑制剂，在口服 JAK 抑制剂治疗控制性骨髓纤维化研究 (COMFORT) 中已证明其优于安慰剂和最佳可用疗法 (BAT)。 COMFORT-II 是一项针对骨髓纤维化患者的随机 (2:1)、开放标签 3 期研究；随机接受 BAT 的患者可能会在方案定义的疾病进展后或主要终点后交叉使用鲁索替尼，从而混淆长期比较。第 48 周时，与接受 BAT 治疗的患者相比，随机接受鲁索替尼治疗的患者中有 28% (41/146) 的脾脏体积减少了 35%（主要终点）（P<0.001）。鲁索替尼组中的 78 名患者 (53.4%) 在任何时候脾脏体积缩小了 35%，5 年（中位数为 3.2 年）时维持缓解的概率为 0.48（95% 置信区间 (CI)，0.35-0.60）。 ruxolitinib 组的中位总生存期尚未达到，而 BAT 组的中位总生存期为 4.1 年。根据意向治疗分析，与 BAT 相比，鲁索替尼的死亡风险降低了 33%（风险比 (HR)=0.67；95% CI，0.44–1.02；P=0.06）；交叉校正 HR 为 0.44（95% CI，0.18–1.04；P=0.06）。随着暴露时间的延长，不良事件的发生率并未出现意外增加。最终分析表明，鲁索替尼的脾脏体积减小在持续治疗中得以维持，并且可能与生存获益相关。
Ruxolitinib is a Janus kinase (JAK) (JAK1/JAK2) inhibitor that has demonstrated superiority over placebo and best available therapy (BAT) in the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies. COMFORT-II was a randomized (2:1), open-label phase 3 study in patients with myelofibrosis; patients randomized to BAT could crossover to ruxolitinib upon protocol-defined disease progression or after the primary end point, confounding long-term comparisons. At week 48, 28% (41/146) of patients randomized to ruxolitinib achieved ⩾35% decrease in spleen volume (primary end point) compared with no patients on BAT (P<0.001). Among the 78 patients (53.4%) in the ruxolitinib arm who achieved ⩾35% reductions in spleen volume at any time, the probability of maintaining response was 0.48 (95% confidence interval (CI), 0.35–0.60) at 5 years (median, 3.2 years). Median overall survival was not reached in the ruxolitinib arm and was 4.1 years in the BAT arm. There was a 33% reduction in risk of death with ruxolitinib compared with BAT by intent-to-treat analysis (hazard ratio (HR)=0.67; 95% CI, 0.44–1.02; P=0.06); the crossover-corrected HR was 0.44 (95% CI, 0.18–1.04; P=0.06). There was no unexpected increased incidence of adverse events with longer exposure. This final analysis showed that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits.