DataSheet_1_Clear Improvement in Real-World Chronic Myeloid Leukemia Survival: A Comparison With Randomized Controlled Trials.docx

Tyrosine kinase inhibitors (TKIs) have been improving the prognosis of patients with chronic myeloid leukemia (CML), but there are still large differences in survival among European countries. This raises questions on the added value of results from population-based studies, which use real-world data, compared to results of randomized controlled trials (RCTs) involving patients with CML. There are also questions about the extent of the findings on RCTs effectiveness for patients in the general population. We compare survival data extracted from our previous systematic review and meta-analysis of CML RCTs with the latest updated population-based survival data of EUROCARE-6, the widest collaborative study on cancer survival in Europe. The EUROCARE-6 CML survival estimated in patients (15–64 years) diagnosed in 2000–2006 vs. 2007–2013 revealed that the prognostic improvement highlighted by RCTs was confirmed in real-world settings, too. The study shows, evaluating for the first time all European regions, that the optimal outcome figures obtained in controlled settings for CML are also achievable (and indeed achieved) in real-world settings with prompt introduction of TKIs in daily clinical practice. However, some differences still persist, particularly in Eastern European countries, where overall survival values are lower than elsewhere, probably due to a delayed introduction of TKIs. Our results suggest an insufficient adoption of adequate protocols in daily clinical practice in those countries where CML survival values remain lower in real life than the values obtained in RCTs. New high-resolution population-based studies may help to identify failures in the clinical pathways followed there.

酪氨酸激酶抑制剂（Tyrosine Kinase Inhibitors, TKIs）虽已改善慢性髓系白血病（Chronic Myeloid Leukemia, CML）患者的预后，但欧洲各国患者的生存结局仍存在显著差异，这引发了学界对两类研究结果附加价值的讨论：一类是采用真实世界数据的基于人群研究的结果，另一类是针对CML患者的随机对照试验（Randomized Controlled Trials, RCTs）的结果。同时，学界也关注RCTs的疗效结论在普通人群中的适用范围。本研究将此前系统综述与荟萃分析中提取的CML RCTs生存数据，与欧洲规模最大的癌症生存协作研究EUROCARE-6的最新更新版基于人群生存数据进行对比。针对2000–2006年与2007–2013年确诊的15–64岁CML患者的EUROCARE-6生存数据分析显示，随机对照试验所揭示的预后改善趋势，在真实世界场景中同样得到验证。本研究首次覆盖欧洲所有区域开展分析，结果表明：在受控试验环境中获得的CML最优生存结局，在日常临床实践中通过及时启用TKIs同样可实现（且已切实达成）。但部分区域仍存在生存结局差异，尤以东欧国家为甚——其总生存期水平低于其他地区，推测原因可能与TKIs应用延迟有关。本研究结果提示，在那些真实世界中CML生存水平仍低于RCTs结果的国家，临床实践中适宜诊疗方案的推广仍存在不足。未来开展高分辨率基于人群的研究，或有助于明确此类地区临床路径中存在的缺陷。