ASCO2014: 唑来膦酸延续治疗乳腺癌骨转移：每4周还是每12周？

唑来膦酸（ZOL）4mg每四周给药（q4 wk）可降低乳腺癌伴骨转移患者骨骼相关事件（SREs）的风险。2014ASCO大会所发布的OPTIMIZE-2研究中，来自美国德克萨斯大学MD安德森癌症中心等机构的研究者希望明确：对于那些先前已接受双膦酸盐注射治疗1年以上的患者，ZOL每12周给药（q12 wk）的疗效及安全性是否非劣于q4 wk给药。结果验证了非劣效性的猜测。研究细节如下：

研究方法：

本研究为一项前瞻性随机双盲多中心对照研究，所纳入的均为女性乳腺癌伴骨转移患者，且在先前10-15个月的治疗中接受超过9剂双膦酸盐（ZOL或帕米膦酸钠）静脉注射治疗。研究者将这些受试者以1：1的比例随机分入ZOL q4 wk组及ZOL q12 wk组，并持续接受为期一年的治疗，其间维持盲法设计。研究主要终点为发生SREs次数≥1的患者比例，即SRE发生率。主要分析为SRE发生率的非劣效性（预设界值10%）。次要终点包括首次发生SRE的时间、骨骼并发症发病率（SMR）、骨痛评分、骨转换指标及安全性。

研究结果：

共有403名患者被随机分入ZOLq4 wk组（n=200）及ZOLq12 wk组（n203）。受试者中位年龄为59岁，基线时各组特征类似。SRE发生率方面，ZOLq4 wk组及q12 wk组分别为22%和23.2%，组间差异为1.2%（95% 置信区间[CI], –7.5%-9.8%;   P = .724）。CI上限（9.8%）低于预设非劣效性边界（10%），提示q12 wk非劣于q4 wk。研究中，两组首次发生SREs的时间类似（HR, 1.06; 95% CI, 0.70-1.60; P = .792），平均SMR亦类似（分别为0.46和0.50; P = .854）。两组骨转换指标较基线时的变化及治疗后出现的不良事件（TEAEs）总体相仿。从数字上看，ZOL q4 wk组肾脏TEAEs高于ZOL q12 wk组（分别为9.6%和7.9%）。另外，q4 wk组报告了2例（1.0%）颚骨坏死（ONJ），而q12 wk未报告。

研究结论：

在接受双膦酸盐静脉注射治疗1年或1年以上的患者中，继续予以ZOL q12 wk治疗1年的效果及安全性非劣于q4 wk组。同时，前者肾脏不良反应更少，且无ONJ病例。

ASCO简评：

Patricia Ganz医生 ASCO大会专家 加州大学洛杉矶分校（UCLA）医学与公共卫生学院

“该研究结果为那些需要长期预防骨折的转移性乳腺癌女性患者带来了福音：她们可以选择接受频率更低的双膦酸盐治疗，同时不用牺牲疗效及安全性。”

医脉通整理报道，转载请注明出处。

会议专题》》》2014年ASCO年会专题报道

原文摘要

Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer: Results of the OPTIMIZE-2 trial.（Abstract #LBA9500^ ）

Authors: Gabriel N. Hortobagyi, Allan Lipton, Helen K. Chew, William John Gradishar, Nicholas P. Sauter, Ramon W. Mohanlal, Ming Zheng, Beth McGrain, Catherine Van Poznak; The University of Texas MD Anderson Cancer Center, Houston, TX; Penn State Hershey Medical Center, Hershey, PA; University of California, Davis, Sacramento, CA; Northwestern University Feinberg School of Medicine, Chicago, IL; Novartis Pharmaceuticals Corporation, East Hanover, NJ; University of Michigan, Ann Arbor, MI

Background: Zoledronic acid (ZOL, 4 mg) every (q) 4 wk reduces the risk of skeletal-related events (SREs) in patients (pts) with bone metastases from breast cancer (BC). The OPTIMIZE-2 trial examined whether ZOL q12 wk was non-inferior to ZOL q4 wk in pts who had previously received monthly IV bisphosphonate (BP) therapy for ~1 year or longer.

Methods: This was a prospective, randomized, double-blind, multicenter trial in female pts with bone metastases from BC who previously received ≥9 doses of IV BP (ZOL or pamidronate) during the first 10-15 months of therapy. Pts were randomized (1:1) to receive ZOL 4 mg IV q4 wk or q12 wk (placebo between ZOL doses to maintain blind) for 1 year. The primary endpoint was the proportion of pts with ≥1 SRE on study (SRE rate). Primary analysis was non-inferiority (pre-defined margin of 10%) for the difference in SRE rates. Secondary endpoints included time to first SRE, skeletal morbidity rate (SMR), bone pain score, change in bone turnover markers, and safety.

Results: 403 pts were randomized to ZOL q4 wk (n = 200) or q12 wk (n = 203). Median age was 59 years, and baseline characteristics were similar between arms. The SRE rate was 22% and 23.2% in the ZOL q4 and q12 wk arms, respectively. The difference in SRE rate between arms was 1.2% (95% CI, –7.5% to 9.8%; P = .724). The upper limit of this 95% CI (9.8%) is less than the predefined margin of 10%, which indicates non-inferiority of ZOL q12 wk vs q4 wk. Times to first on-study SRE (HR, 1.06; 95% CI, 0.70 to 1.60; P = .792) were similar in the ZOL q4 and q12 wk arms, and mean SMRs were also similar (0.46 vs 0.50, respectively; P = .854). Overall, changes from baseline in bone turnover markers, and the incidence of treatment-emergent adverse events (TEAEs), were similar in the 2 arms. Numerically more renal TEAEs were reported in the ZOL q4 wk vs q12 wk arm (9.6% vs 7.9%, respectively). Two cases (1.0%) of osteonecrosis of the jaw (ONJ) were reported in the q4 wk arm.

Conclusions: Among pts who had received monthly IV BP therapy for 1 year or longer, the efficacy of continuing ZOL for an additional year at q12 wk was non-inferior to ZOL q4 wk. Fewer renal AEs and none of the ONJ events were observed in the ZOL q12 wk vs ZOL q4 wk arm.


原贴地址：
http://news.medlive.cn/all/info-progress/show-62872_53.html

如果这个研究成立，对于所有的骨转治疗是否有所借鉴？

希望对于肺癌骨转的也有同样的意义，福音！

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