Raje N, Vadhan-Raj S, Willenbacher W, Terpos E, Hungria V, Spencer A, Alexeeva Y, Facon T, Stewart A K, Feng A, Braun A, Balakumaran A, Roodman G D
Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Blood Cancer J. 2016 Jan 8;6(1):e378. doi: 10.1038/bcj.2015.96.
In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P=0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P=0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P=0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial.
在一项针对1776例患有骨转移且伴有实体瘤或多发性骨髓瘤的患者进行的地诺单抗与唑来膦酸对比的3期试验中，就预防骨相关事件的主要终点而言，地诺单抗优于唑来膦酸。两组的总生存期无差异；然而，对多发性骨髓瘤亚组患者（n = 180）进行的一项临时总生存期分析显示，唑来膦酸更具优势（风险比（HR）2.26；95%置信区间（CI）1.13 - 4.50；P = 0.014）。在本分析中，我们发现两组在基线风险特征方面存在失衡。使用Cox模型估计双侧95%CI的HR。在协变量分析中进行调整后，CI跨过了1（HR 1.86；95%CI 0.90 - 3.84；P = 0.0954）。此外，我们发现唑来膦酸组因失访和撤回同意而提前退出的比例更高；考虑到这些因素后，HR为1.31（95%CI 0.80 - 2.15；P = 0.278）。总之，该试验中多发性骨髓瘤患者的生存结果存在混淆，最终将通过正在进行的3期试验得以解决。
