Joan Karnell Cancer Center, Philadelphia, PA 19106, USA.
J Clin Oncol. 2011 Mar 20;29(9):1125-32. doi: 10.1200/JCO.2010.31.3304. Epub 2011 Feb 22.
This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma.
Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression).
Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading.
Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.
本研究比较了地舒单抗（一种完全人源化单克隆抗核因子 κB 配体受体激活剂抗体）与唑来膦酸（ZA）在预防或延迟晚期癌症伴骨转移（不包括乳腺癌和前列腺癌）或多发性骨髓瘤患者骨骼相关事件（SRE）中的作用。
符合条件的患者以双盲、双模拟设计随机分配，每月接受皮下注射地舒单抗 120mg（n=886）或静脉注射 ZA 4mg（根据肾功能调整剂量；n=890）。强烈推荐每日补充钙和维生素 D。主要终点是首次研究相关 SRE（病理性骨折、骨放疗或手术、或脊髓压迫）的时间。
地舒单抗在延迟首次研究相关 SRE 的时间方面非劣效于 ZA（风险比，0.84；95%置信区间，0.71 至 0.98；P=0.0007）。尽管地舒单抗在延迟首次研究相关 SRE 时间（未校正 P=0.03；校正多重性 P=0.06）或首次和随后（多次）SRE 时间（发生率比，0.90；95%置信区间，0.77 至 1.04；P=0.14）方面无统计学优势，但具有优势趋势。两组的总生存和疾病进展相似。地舒单抗更常发生低钙血症。两组的颌骨坏死发生率相似。ZA 首次剂量后更常发生急性期反应，以及根据国家癌症研究所不良事件通用毒性标准进行的肾功能不良事件和血清肌酐升高。
地舒单抗在预防或延迟晚期癌症伴骨转移或多发性骨髓瘤患者首次研究相关 SRE 方面非劣效（具有优势趋势）于 ZA。地舒单抗是一种潜在的新型治疗选择，具有皮下给药的便利性，且无需进行肾功能监测或剂量调整。
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