Zeidan Amer M, Davidoff Amy J, Long Jessica B, Hu Xin, Wang Rong, Ma Xiaomei, Gross Cary P, Abel Gregory A, Huntington Scott F, Podoltsev Nikolai A, Hajime Uno, Prebet Thomas, Gore Steven D
Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT, USA.
Br J Haematol. 2016 Dec;175(5):829-840. doi: 10.1111/bjh.14305. Epub 2016 Sep 21.
The hypomethylating agents (HMAs) azacitidine and decitabine are both approved for treatment of myelodysplastic syndromes (MDS) in the USA. In Europe, decitabine is not approved due to lack of survival advantage in randomized trials. The two drugs have not been compared in clinical trials. We identified patients diagnosed with MDS between 2004 and 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in the USA who received ≥ 10 doses of either HMA. We estimated survival from HMA initiation with Kaplan-Meier methods and used multivariate Cox proportional hazards models to adjust for covariates. Analyses controlled for histological subtype and we conducted a subset analysis limited to patients with refractory anaemia with excess blasts (RAEB). In 2025 HMA-treated patients, median survival was 15 months with no difference in survival based on the HMA received in adjusted analysis (decitabine versus azacitidine, hazard ratio = 1·06, 95% confidence interval: 0·94-1·19, P = 0·37). For RAEB patients (n = 523), median survival was 12 months, with no significant difference based on HMA received. No significant survival difference was found between azacitidine and decitabine in patients with MDS, including RAEB. Importantly, population-based survival of azacitidine-treated RAEB patients was substantially shorter than in the AZA-001 clinical trial (11 versus 24·5 months).
去甲基化药物阿扎胞苷和地西他滨在美国均被批准用于治疗骨髓增生异常综合征（MDS）。在欧洲，由于随机试验中缺乏生存优势，地西他滨未获批准。这两种药物尚未在临床试验中进行比较。我们从美国监测、流行病学和最终结果（SEER）-医疗保险链接数据库中识别出2004年至2011年间被诊断为MDS且接受了≥10剂任何一种去甲基化药物治疗的患者。我们用Kaplan-Meier方法估计从开始使用去甲基化药物起的生存率，并使用多变量Cox比例风险模型对协变量进行调整。分析对组织学亚型进行了控制，并且我们进行了一项仅限于难治性贫血伴原始细胞增多（RAEB）患者的亚组分析。在225例接受去甲基化药物治疗的患者中，中位生存期为15个月，在调整分析中，基于所接受的去甲基化药物（地西他滨与阿扎胞苷），生存率无差异（风险比=1.06，95%置信区间：0.94-1.19，P=0.37）。对于RAEB患者（n=523），中位生存期为12个月，基于所接受的去甲基化药物无显著差异。在MDS患者（包括RAEB）中，阿扎胞苷和地西他滨之间未发现显著的生存差异。重要的是，基于人群的阿扎胞苷治疗的RAEB患者的生存期明显短于AZA-001临床试验中的生存期（11个月对24.5个月）。
