医脉通编译整理，转载请务必注明出处。
2016年6月3日，一年一度的美国临床肿瘤学会（AmericanSocietyofClinicalOncology, ASCO）年会在芝加哥召开。本次大会将吸引30000名全世界的肿瘤领域专家学者和参会人员，会议摘要收录了多个我国学者主导的肿瘤前沿研究。
北京解放军307医院乳腺肿瘤内科主任江泽飞教授带领的国内团队开展了一项随机双盲、双模拟的Ⅲ期临床研究，比较狄诺塞麦（Denosumab, DmAb）和唑来膦酸（Zoledronic Acid, ZA）在中国实体瘤骨转移患者中的治疗作用和安全性，为DmAb在恶性肿瘤骨转移后骨相关事件（SERs）预防领域的全球研究提供亚裔人种数据。
骨是恶性肿瘤尤其是乳腺癌、前列腺癌和肺癌等恶性实体瘤常见的转移部位，65%—80%的乳腺癌和前列腺癌以及 30%—40%的肺癌会发生骨转移。恶性实体瘤骨转移和多发性骨髓瘤常引起严重的骨疼痛和骨相关事件（skeletal-relatedevents, SREs）。临床研究时SREs定义为：骨痛加剧或出现新的骨痛、病理性骨折(椎体骨折、非椎体骨折)、椎体压缩或变形、脊髓压迫、骨放疗后症状(因骨痛或防治病理性骨折或脊髓压迫)及高钙血症。
唑来膦酸是第3代双磷酸盐，可联合抗肿瘤治疗以预防或延迟SREs的发生，改善患者的生活质量，延长生存时间。但唑来膦酸有一定的肾毒性，限制了使用。狄诺塞麦是一种特异性靶向核因子-κB受体活化因子配体（RANK-L）的完全人源化单克隆抗体（IgG2单抗），可以阻止RANKL和其受体物质结合，抑制破骨细胞活化和发展，减少骨吸收，增加骨矿物质密度，且不依赖肾脏代谢。
摘要编号：10116
时间：6月6日，下午1:00-4:30
报告形式：壁报展示
患者入组主要标准：
◆年龄≥18岁，
◆组织学或细胞学确诊为实体瘤，种族为华裔。
◆影像学检查（X线、CT、MRI）确认至少一处骨转移
◆孕龄期妇女必须在初次治疗前7天内检测未怀孕，且同意在治疗期间进行有效避孕
◆ECOG PS≤2
◆肝肾器官及血液功能足够
◆期望寿命≥6个月
研究共纳入485名恶性实体瘤患者，按2:1随机分配进入两治疗组，其中DmAb组326例，ZA组159例。DmAb组皮下注射120mg每四周一次， ZA组静脉给药4mg每四周一次，治疗49周，随访至73周。
主要终点是尿液中Ⅰ型胶原交联氨基末端肽/肌酐（uNTx/uCr）变化。次要终点是骨源性碱性磷酸酶（S-BALP）变化和至首次发生SRE时间。
结果
90%的患者或完成了治疗，或在计划数据截止时退出。入组患者基线数据：
◆中位年龄为53.9岁，女性占67%，中国人占93%。
◆乳腺癌占50%，非小细胞肺癌占27%。
◆13周后与基线相比，DmAb组uNTx/uCr下降81.9%，ZA组下降75.2%。
◆13周后与基线相比，DmAb组S-BALP下降36.8%，ZA组下降30.3%。
◆接受治疗1年内，DmAb组的SRE发生率虽然低于ZA组（4.9% vs 6.3%），但无统计学差异。
◆DmAb组和ZA组不良反应发生率接近，分别为89% vs 91%。
◆最常见的不良反应在两组中分别为贫血（25% vs 24%）、血细胞计数下降（21% vs 24%）、发热（13% vs 21%）。
◆严重不良反应总体发生率DmAb组为14%，ZA组为9%。
结论
由于狄诺塞麦在药物机制方面的良好特点，该研究的设计初衷就是检验狄诺塞麦对比唑来膦酸的优效性。而研究结果也证实了新型药物狄诺塞麦在中国人群中的良好效果，在安全性方面也稍优于唑来膦酸，未来如果狄诺塞麦在国内上市，将会为晚期恶性肿瘤骨转移患者提供新的治疗选择。
会议专题》》》2016年ASCO年会专题报道
摘要阅读
Abstract No: 10116
Efficacyand safety of denosumab from a phase III, randomized, active-controlled studycompared with zoledronic acid in patients of Asian ancestry with bonemetastases from solid tumors
Session: Patient and SurvivorCare
Type: Poster Session
Author(s): Zefei Jiang, ZhiminShao, Qingyuan Zhang,et al.
Background:This phase IIIdouble-blind study was conducted to provide bridging data to the availableefficacy and safety data of denosumab (DmAb) from global skeletal-relatedevents (SRE)-prevention studies, by comparing DmAb with zoledronic acid(ZA).
Methods:Patients aged≥18 years who had a confirmed solid tumor, evidence of ≥1 bone metastasis andECOG score 0-2 were enrolled. Patients were randomized (2:1) to receive eitherDmAb 120 mg subcutaneously every 4 weeks (Q4W) or ZA 4 mg intravenously Q4W for49 weeks (wks) and are being followed up to Wk 73. The primary endpoint waspercent change in urinary amino-terminal cross-linking telopeptide of type Icollagen, corrected for urine creatinine (uNTx/uCr) from baseline (BL) to 13wks. Other endpoints were percent change in bone-specific alkaline phosphatase(S-BALP) from BL to 13 wks and time to first on-study SRE. Safety andtolerability were assessed including collecting all adverse events (AEs) andperforming vital signs measurement and a standard panel of laboratorytests.
Results:A total of 485(DmAb=326, ZA=159) pts were randomized; 90% of pts had either completed thestudy or withdrawn by planned data cut-off (29 February 2016). Mean (SD) age ofpts was 53.9 (11.38) years; 67% pts were women, 93% Chinese, 50% had breastcancer and 27% had non-small cell lung cancer. The mean change in uNTx/uCr fromBL to Wk 13 was -81.9% for DmAb and -75.2% for ZA (ANCOVA; p<0.0001). Themedian change in S-BALP from BL to Wk 13 was -36.8% (DmAb) and -30.3% (ZA)(p=0.027). Rate of developing any on-study SRE within the first year afterinitializing treatment was lower in pts receiving DmAb vs ZA (4.9% vs 6.3%)without statistical significance. Incidence of AEs was similar in DmAb and ZAgroups (89% vs 91%), with most common AEs being anemia (25% vs 24%), whiteblood cell count decreased (21% vs 24%), and pyrexia (13% vs 21%); overallincidence of serious AEs: 14% vs 9%. One serious AE (muscular weakness) wasreported as related to study treatment.
Conclusions:DmAb was foundto be superior than ZA in reducinguNTx/uCr in overall and Chinese pts. No newsafety concerns were identified with DmAb. Clinical trial information:NCT01920568.
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医脉通编译自：Zefei Jiang,et al. Efficacyand safety of denosumab from a phase III, randomized, active-controlled studycompared with zoledronic acid in patients of Asian ancestry with bonemetastases from solid tumors.J Clin Oncol 34, 2016 (suppl;abstr 10116).
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1.乔光磊等.肿瘤,2013,01:48-57.
2.江泽飞等.乳腺癌骨转移和骨相关疾病临床诊疗专家共识(2014版)[J].中华医学杂,2015,95(4):241-247.
