Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma
Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma
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DOI：
10.1200/jco.2010.31.3304
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发表时间：
2011-03-20
影响因子：
45.3
通讯作者：
Yeh, Howard
中科院分区：
文献类型：
--
作者：
Henry, David H.;Costa, Luis;Yeh, Howard
本研究比较了核因子kappa-B配体抗体的全人类抗受体单抗激活剂迪诺单抗与唑来膦酸(ZA)在延缓或预防晚期癌症和骨转移(不包括乳腺和前列腺癌)或骨髓瘤患者骨骼相关事件(SRE)方面的作用。患者和方法采用双盲双模拟设计，将符合条件的患者随机分为两组，每月皮下注射地诺单抗120 mg(n=886)或静脉注射ZA 4 mg(根据肾功能损害调整剂量；n=890)。强烈建议每天补充钙和维生素D。主要终点是首次进行SRE研究的时间(病理性骨折、放射治疗或手术或脊髓压迫)。结果Denosumab在延迟首次进行SRE研究的时间方面不逊于ZA(风险比，0.84；95%CI，0.71~0.98；P=.0007)。尽管在方向性上有利，在延迟首次研究SRE的时间(P=0.03未调整；经多样性调整P=0.06)或首次和后续(多次)SRE的时间(比率，0.90；95%可信区间，0.77至1.04；P=.14)方面，Denosumab在统计学上并不优于ZA。两组之间的总体存活率和疾病进展相似。使用Denosumab时，低血钙症的发生率更高。在两组患者中，颌骨坏死的发生率都很低。ZA在首剂后的急性时相反应、肾脏不良事件和血肌酐升高的发生率高于ZA。结论Denosumab在预防或延迟晚期癌症骨转移或骨髓瘤患者首次研究中的SRE方面并不逊于ZA(倾向于优于ZA)。Denosumab是一种潜在的新的治疗选择，皮下给药方便，不需要肾脏监测或剂量调整。J Clin Oncol29：1125-1132。(C)2011年美国临床肿瘤学会
PurposeThis 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.Patients and MethodsEligible 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).ResultsDenosumab 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.ConclusionDenosumab 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. J Clin Oncol 29: 1125-1132. (C) 2011 by American Society of Clinical Oncology