Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Eur J Cancer. 2012 Nov;48(16):3082-92. doi: 10.1016/j.ejca.2012.08.002. Epub 2012 Sep 10.
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.
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.
Denosumab was superior to zoledronic acid in delaying time to first on-study SRE by a median 8.21months, 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).
Denosumab was superior to zoledronic acid in preventing SRE with favourable safety and convenience in patients with bone metastases from advanced cancer.
晚期癌症骨转移患者常发生骨骼相关事件（SRE），导致严重疼痛和发病率。地舒单抗是一种完全人源化单克隆抗体，可抑制核因子 κB 受体激活配体（RANKL），是一种新型的骨靶向药物，与双膦酸盐唑来膦酸相比，具有独特的作用机制，可预防 SRE。本预先计划的分析评估了地舒单抗与唑来膦酸在三项关键研究中的疗效和安全性。
将来自三项设计相同、随机、双盲、活性对照、3 期临床试验的乳腺癌、前列腺癌、其他实体瘤或多发性骨髓瘤患者的个体患者数据进行合并。终点包括首次 SRE 时间、首次和随后（多次）SRE 时间、不良事件、疾病进展时间和总生存时间。
地舒单抗可显著延迟首次研究期间 SRE 的发生时间，中位数为 8.21 个月，使首次 SRE 风险降低 17%（风险比，0.83[95%置信区间（CI）：0.76-0.90]；P<0.001）。首次和多次事件以及各患者亚组（既往 SRE 状态；年龄）均显示出疗效。两种治疗方法的疾病进展和总生存时间相似。与唑来膦酸不同，地舒单抗无需根据肾功能监测或调整剂量/停药，也不会发生急性期反应。地舒单抗更易引起低钙血症。颌骨坏死的发生率相似（P=0.13）。
地舒单抗在预防 SRE 方面优于唑来膦酸，且在晚期癌症骨转移患者中具有良好的安全性和便利性。
