Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials
Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials
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DOI：
10.1016/j.ejca.2012.08.002
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发表时间：
2012-11-01
影响因子：
8.4
通讯作者：
Jun, Susie
中科院分区：
文献类型：
--
作者：
Lipton, Allan;Fizazi, Karim;Jun, Susie
背景资料：晚期癌症骨转移的患者经常会发生肿瘤相关事件（SRE），导致严重的疼痛和发病率。Denosumab是一种抑制RANK配体（RANKL）的全人源单克隆抗体，是一种新型骨靶向药物，与双膦酸盐唑来膦酸相比具有不同的作用机制，可预防SRE。这种预先计划的分析评估的疗效和安全性的狄诺塞麦与唑来膦酸在三个关键study.Methods：患者水平的数据从三个相同的设计，随机，双盲，活性对照，3期试验乳腺癌，前列腺癌，其他实体瘤或多发性骨髓瘤患者合并。终点包括至首次SRE的时间、至首次和后续SRE的时间研究结果：地舒单抗在延迟首次研究期间SRE的时间（中位数为8.21个月）方面上级于唑来膦酸，使首次SRE的风险降低17%（危险比，0.83 [95%置信区间（CI）：0.76-0.90]; P < 0.001）。在首起和多起事件以及各患者亚组（既往SRE状态;年龄）中证实了疗效。两种治疗之间的疾病进展和总生存期相似。与唑来膦酸相比，Denosumab不需要根据肾脏状态进行监测或剂量调整/停药，并且与急性期反应无关。低钙血症在地舒单抗组更常见。结论：地舒单抗在预防晚期肿瘤骨转移患者SRE方面上级唑来膦酸，且安全、方便。(C)2012爱思唯尔有限公司保留所有权利。
Background: Patients with bone metastases from advanced cancer often experience skeletal-related events (SRE), which cause substantial pain and morbidity. Denosumab, a fully human monoclonal antibody that inhibits RANK Ligand (RANKL), is a novel bone-targeted agent with a distinct mechanism of action relative to the bisphosphonate zoledronic acid, for prevention of SRE. This pre-planned analysis evaluates the efficacy and safety of denosumab versus zoledronic acid across three pivotal studies.Methods: Patient-level data from three identically designed, randomised, double-blind, active-controlled, phase 3 trials of patients with breast cancer, prostate cancer, other solid tumours or multiple myeloma were combined. End-points included time to first SRE, time to first and subsequent (multiple) SRE, adverse events, time to disease progression and overall survival.Findings: Denosumab was superior to zoledronic acid in delaying time to first on-study SRE by a median 8.21 months, reducing the risk of a first SRE by 17% (hazard ratio, 0.83 [95% confidence interval (CI): 0.76-0.90]; P < 0.001). Efficacy was demonstrated for first and multiple events and across patient subgroups (prior SRE status; age). Disease progression and overall survival were similar between the treatments. In contrast to zoledronic acid, denosumab did not require monitoring or dose modification/withholding based on renal status, and was not associated with acute-phase reactions. Hypocalcaemia was more common for denosumab. Osteonecrosis of the jaw occurred at a similar rate (P = 0.13).Conclusion: Denosumab was superior to zoledronic acid in preventing SRE with favourable safety and convenience in patients with bone metastases from advanced cancer. (C) 2012 Elsevier Ltd. All rights reserved.