Aphase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma
Aphase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma
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DOI：
10.1182/blood-2012-05-425934
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发表时间：
2012-10-04
期刊：
影响因子：
20.3
通讯作者：
Jagannath, Sundar
中科院分区：
文献类型：
--
作者：
Siegel, David S.;Martin, Thomas;Jagannath, Sundar
Carfilzomib是新一代选择性蛋白酶体抑制剂，用于治疗复发和难治性多发性骨髓瘤。在这项开放标签、单臂2期研究（PX-171-003-A1）中，患者在第1周期接受单药carfilzomib 20mg /m(2)静脉注射，每周两次，共3周，然后接受27mg /m(2)治疗（部分缓解）。次要终点包括临床获益、反应率（>=最小反应）、反应持续时间、无进展生存期、总生存期和安全性。共有266例患者可进行安全性评估，257例可进行有效性评估；95%对末次治疗难治性；80%的患者对硼替佐米和来那度胺都难治或不耐受。患者既往接受治疗的中位数为5条线，包括硼替佐米、来那度胺和沙利度胺。总缓解率为23.7%，中位缓解持续时间为7.8个月。中位总生存期为15.6个月。不良事件（ae）可控，无累积毒性。常见的不良事件有疲劳（49%）、贫血（46%）、恶心（45%）和血小板减少（39%）。33例（12.4%）患者出现周围神经病变，主要为1级或2级。33例（12.4%）患者因AE退出治疗。在这些经过大量预处理的人群中，持久的反应和可接受的耐受性表明卡非佐米有可能提供有意义的临床益处。该试验在www.clinicaltrials.gov注册为#NCT00511238。（血液杂志；2012;120(14):2817-2825）
Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfilzomib 20 mg/m(2) intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m(2) for = partial response). Secondary end-points included clinical benefit response rate (>= minimal response), duration of response, progression-free survival, overall survival, and safety. A total of 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide. Overall response rate was 23.7% with median duration of response of 7.8 months. Median overall survival was 15.6 months. Adverse events (AEs) were manageable with-out cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirty-three patients (12.4%) experienced peripheral neuropathy, primarily grades 1 or 2. Thirty-three patients (12.4%) withdrew because of an AE. Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. This trial was registered at www.clinicaltrials.gov as #NCT00511238. (Blood. 2012; 120(14): 2817-2825)