狄诺塞麦与唑来膦酸治疗恶性实体瘤骨转移和多发性骨髓瘤骨相关事件的疗效和安全性的比较:一项Meta分析  

Comparison of efficacy and safety of denosumab versus zoledronic acid for treating skeletal-related events caused by bone metastasis in patients with maligmant solid tumors and multiple myeloma: A Meta-analysis of randomized controlled trials

作　　者：乔光磊[1] 郑水儿[1] 祁伟祥[1] 闵大六[1] 沈赞[1] 姚阳[1] 

机构地区：[1]上海交通大学附属第六人民医院肿瘤内科,上海200233

出　　处：《肿瘤》2013年第1期48-57,共10页Tumor

基　　金：国家自然科学基金资助项目(编号:81001192;81172105)

摘　　要：目的:评价狄诺塞麦与唑来膦酸治疗恶性实体瘤骨转移及多发性骨髓瘤引起的骨相关事件(skeletal-related events,SREs)的疗效和安全性。方法:利用计算机检索Cochrane Library、PubMed、EMBase、中国知网、万方和维普等数据库。按照文献纳入标准和排除标准选择临床随机对照试验(randomized controlled trial,RCT)文献,评价文献质量,并提取资料,应用RevMan5.0软件进行Meta分析。结果:最终纳入3项RCT,共包括5723例患者。Meta分析结果显示,狄诺塞麦组与唑来膦酸组相比,明显延迟至首次发生SREs的时间,风险比(hazard ratio,HR)降低17%(HR=0.83,95%CI:0.76～0.90,P<0.0001),平均延迟时间为4.3个月;明显延迟随后发生SREs的时间,比率比(rate ratio,RR)降低17%(RR=0.83,95%CI:0.76～0.90,P<0.00001)。两组的总生存时间(overall survival,OS)(HR=0.98,95%CI:0.91～1.06,P=0.64)、无进展生存时间(progression-free survival,PFS)(HR=1.01,95%CI:0.95～1.08,P=0.72)、不良事件(adverse events,AEs)发生率[比值比(odds ratio,OR)=0.86,95%CI:0.65～1.15,P=0.31]、严重不良事件(serious AEs,SAEs)发生率(OR=0.96,95%CI:0.87～1.07,P=0.49)、恶心发生率(OR=0.97,95%CI:0.86～1.08,P=0.55)、疲劳发生率(OR=1.01,95%CI:0.83～1.22,P=0.94)、背痛发生率(OR=0.95,95%CI:0.84～1.07,P=0.36)和颌骨坏死发生率(osteonecrosis of the jaw,ONJ)(OR=1.42,95%CI:0.95～2.13,P=0.09)差异无统计学意义。狄诺塞麦组的贫血(OR=0.86,95%CI:0.76～0.96,P=0.009)、肾毒性相关AEs(OR=0.73,95%CI:0.55～0.96,P=0.02)和急性期反应(OR=0.37,95%CI:0.32～0.43,P<0.00001)发生率均较唑来膦酸组低,而低钙血症发生率(OR=2.05,95%CI:1.66～2.53,P<0.00001)较高。结论:狄诺塞麦在延迟恶性实体瘤骨转移及多发性骨髓瘤引起的SREs方面优于唑来膦酸。在安全性方面,狄诺塞麦的贫血、肾毒性相关AEs和急性期反应发生率均明显低于唑来膦酸,但低钙血症的发生率较高。Objective： To assess the efficacy and safety of denosumab compared with zoledronic acid in treatment of SREs （skeletal-related events） caused by bone metastasis of malignant solid tumors and multiple myeloma. Methods： A computer-based online search was performed by using Cochrane Library, PubMed, EMBase, CNKI （China National Knowledge Infrastructure）, Wanfang database and VlP database. Studies reporting RCT （randomized controlled trial） in accordance with the inclusion and exclusion criteria were included. Quality of the studies was assessed with Jadad score. The results were independently extracted by two reviewers. The data were analyzed using RevMan 5.0 software. Resuhs： A total of three RCTs including 5 723 patients were involved in this Meta-analysis. Analysis of RCTs showed that denosumab was superior to zoledronic acid in delaying the time to the onset of first SRE during study period by 1 7% [HR （hazard ratio） =0.83, 95% CI （confidence interval）： 0.76-0.90; P 〈 0.000 1]. Mean time of delay to the onset of first SRE was 4.3 months. Denosumab was also superior to zoledronic acid in delaying the time to first and subsequent SREs during study period by 17% [RR （rate ratio） = 0.83, 95% CI： 0.76-0.90; P 〈 0.000 01]. There were no significant differences in OS （overall survival） （HR = 0.98, 95% CI： 0.91-1.06; P = 0.64）, PFS （progression- free survival） （HR = 1.01, 95% Ch 0.95-1.08; P = 0.72） and incidence rates of AEs （adverse events） [OR （odds ratio） = 0.86, 95% Ch 0.65-1.15; P = 0.31], SAEs （serious AEs） （OR = 0.96, 95% Ch 0.87-1.07; P = 0.49）, nausea （OR = 0.97, 95% Ch 0.86-1.08; P = 0.55）, fatigue （OR = 1.01, 95% Ch 0.83-1.22; P = 0.94）, back pain （OR = 0.95, 95% Ch 0.84-1.07; P = 0.36） and ONJ （osteonecrosis of the jaw） （OR = 1.42, 95% CI： 0.95-2.13; P = 0.09） between denosumab group and zoledronic acid group. But denosumab group had lower incidence rates of anemia （OR = 0.86, 95% Ch 0.76-0.96; P = 0.009）, rena

关 键 词：骨转移 肿瘤 多发性骨髓瘤 狄诺塞麦 唑来膦酸 骨相关事件 随机对照试验 META分析 

分 类 号：R733.3[医药卫生—肿瘤]