Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis A Randomized Clinical Trial
Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis A Randomized Clinical Trial
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DOI：
10.1001/jamaoncol.2015.1590
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发表时间：
2015-08-01
期刊：
影响因子：
28.4
通讯作者：
Tefferi, Ayalew
中科院分区：
文献类型：
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作者：
Pardanani, Animesh;Harrison, Claire;Tefferi, Ayalew
重要意义骨髓纤维化(MF)是一种bcr-abl阴性的骨髓增生性肿瘤，以贫血、脾肿大、虚弱的躯体症状和生存期缩短为特征。目的评价非德拉替尼治疗原发或继发性(真性红细胞增多症后或原发性血小板增多症后)MF患者的有效性和安全性。DESIGN，设置和参与者在24个国家的94个地点进行的双盲、随机、安慰剂对照的3期研究，其中289名成人患者(>；=18岁)中危或高危原发MF、真性红细胞增多症后MF或原发性血小板增多症后MF在2011年12月至2012年9月期间被随机分配给每日一次口服非卓替尼，剂量为400 mg或500 mg，或安慰剂，持续至少6个4周周期。主要终点是在24周时的脾反应(通过磁共振成像或计算机断层扫描确定的脾体积比基线缩小35%)，并在4周后得到证实。结果非屈拉替尼400 mg和500 mg组96例患者中有35例(36%[95%可信区间，27%~46%])和39例(40%[95%可信区间，30%~50%])达到了主要终点，而安慰剂组96例患者中有1例(1%[95%可信区间，0%~3%])达到了主要终点(P
IMPORTANCE Myelofibrosis (MF) is a BCR-ABL-negative myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating constitutional symptoms, and shortened survival. Fedratinib, a JAK2-selective inhibitor, previously demonstrated clinically beneficial activity in patients with MF in early-phase trials.OBJECTIVE To evaluate the efficacy and safety of fedratinib therapy in patients with primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF.DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, placebo-controlled phase 3 study in 94 sites in 24 countries in which 289 adult patients (>= 18 years of age) with intermediate-2 or high-risk primaryMF, post-polycythemia vera MF, or post-essential thrombocythemia MF were randomly assigned between December 2011 and September 2012 to once-daily oral fedratinib, at a dose of 400mg or 500mg, or placebo, for at least 6 consecutive 4-week cycles.MAIN OUTCOMES AND MEASURES The primary end point was spleen response (>= 35% reduction in spleen volume from baseline as determined by magnetic resonance imaging or computed tomography) at week 24 and confirmed 4 weeks later. The main secondary end point was symptom response (>= 50% reduction in total symptom score, assessed using the modified Myelofibrosis Symptom Assessment Form).RESULTS The primary end point was achieved by 35 of 96 (36%[95% CI, 27%-46%]) and 39 of 97 (40% [95% CI, 30%-50%]) patients in the fedratinib 400-mg and 500-mg groups, vs 1 of 96 (1% [95% CI, 0%-3%]) in the placebo group (P