Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy
Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy
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DOI：
10.1182/blood-2014-03-560557
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发表时间：
2014-08-28
期刊：
影响因子：
20.3
通讯作者：
Maertens, Johan
中科院分区：
文献类型：
--
作者：
Doehner, Hartmut;Luebbert, Michael;Maertens, Johan
老年急性髓系白血病（AML）患者的治疗结果仍然不佳。这项针对不适合强化诱导治疗的 AML 患者的随机 2 期试验比较了低剂量阿糖胞苷 (LDAC) 联合或不联合 volasertib（一种高效、选择性的 polo 样激酶抑制剂）。 87 名患者（中位年龄 75 岁）在第 1-10 天接受 LDAC 20 mg 每日两次皮下注射，或每 4 周在第 1 + 15 天皮下注射 LDAC + volasertib 350 mg IV。 LDAC + volasertib 的缓解率（完全缓解和血细胞计数不完全恢复的完全缓解）高于 LDAC（31.0% vs 13.3%；比值比，2.91；P = .052）。在所有遗传组中观察到 LDAC + volasertib 组的反应，包括 14 名细胞遗传学不良的患者中的 5 名。与 LDAC 相比，LDAC + volasertib 的中位无事件生存期显着延长（5.6 个月与 2.3 个月；风险比，0.57；95% 置信区间，0.35-0.92；P = 0.021）；中位总生存期分别为 8.0 个月和 5.2 个月（风险比，0.63；95% 置信区间，0.40-1.00；P = .047）。 LDAC + volasertib 导致不良事件发生频率增加，其中最明显的是中性粒细胞减少性发热/感染和胃肠道事件；第 60 天 + 90 天死亡率没有增加。这项研究在 www.clinicaltrials.gov 上注册为#NCT00804856。
Treatment outcomes for older patients with acute myeloid leukemia (AML) have remained dismal. This randomized, phase 2 trial in AML patients not considered suitable for intensive induction therapy compared low-dose cytarabine (LDAC) with or without volasertib, a highly potent and selective inhibitor of polo-like kinases. Eighty-seven patients (median age 75 years) received LDAC 20 mg twice daily subcutaneously days 1-10 or LDAC + volasertib 350 mg IV days 1 + 15 every 4 weeks. Response rate (complete remission and complete remission with incomplete blood count recovery) was higher for LDAC + volasertib vs LDAC (31.0% vs 13.3%; odds ratio, 2.91; P = .052). Responses in the LDAC + volasertib arm were observed across all genetic groups, including 5 of 14 patients with adverse cytogenetics. Median event-free survival was significantly prolonged by LDAC + volasertib compared with LDAC (5.6 vs 2.3 months; hazard ratio, 0.57; 95% confidence interval, 0.35-0.92; P = .021); median overall survival was 8.0 vs 5.2 months, respectively (hazard ratio, 0.63; 95% confidence interval, 0.40-1.00; P = .047). LDAC + volasertib led to an increased frequency of adverse events that was most pronounced for neutropenic fever/infections and gastrointestinal events; there was no increase in the death rate at days 60 + 90. This study was registered at www.clinicaltrials.gov as #NCT00804856.