The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030, USA.
J Clin Oncol. 2011 Aug 10;29(23):3173-8. doi: 10.1200/JCO.2010.33.4169. Epub 2011 Jul 11.
Different definitions of progression-free survival (PFS) and event-free survival (EFS) may result in perceived differences in outcomes with tyrosine kinase inhibitor (TKI) therapies in chronic myelogenous leukemia (CML).
We analyzed the outcome of 435 patients with early chronic-phase, Philadelphia chromosome-positive CML treated with imatinib (n = 281), nilotinib (n = 78), and dasatinib (n = 76) using definitions of PFS and EFS used in the International Randomized Study of Interferon Versus STI571 (IRIS), Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENEST-nd), Dasatinib Versus Imatinib Study in Treatment-Naïve CML Patients (DASISION), and MD Anderson Cancer Center (MDACC) trials. Definitions for EFS-IRIS, time without progression in ENEST-nd, PFS-DASISION, and EFS-MDACC were as previously reported. The EFS-MDACC considered an event any instance of toxicity or death from any cause on or off therapy (if not counted before death as progression/event).
Of the 435 patients, 123 (28%) were taken off TKI therapy (resistance/loss of response, n = 33; blastic phase on TKI therapy, n = 6; intolerance/toxicity, n = 29; other causes, n = 55). Thirty-three patients (7.6%) have died; eight patients died on TKI therapy, two patients died within 60 days of being off TKIs, and 23 patients died after being off TKIs for more than 60 days. Of the 33 deaths, 19 deaths (eight deaths on TKI, two deaths within 60 days, and nine deaths off for resistance/relapse/transformation) would be counted as progression/events on the IRIS/ENEST-nd/DASISION studies, whereas 14 deaths would be censored at time off TKI. On the basis of the four definitions used by IRIS, ENEST-nd, DASISION, and MDACC trials, the corresponding 5-year PFS/EFS rates were 96%, 90%, 89%, and 81%.
Uniform definitions of PFS and EFS are needed to compare the long-term efficacy and potential use of different TKIs in CML.
不同的无进展生存期（PFS）和无事件生存期（EFS）定义可能导致慢性髓性白血病（CML）酪氨酸激酶抑制剂（TKI）治疗的结果出现差异。
我们分析了 435 例接受伊马替尼（n=281）、尼洛替尼（n=78）和达沙替尼（n=76）治疗的早期慢性期费城染色体阳性 CML 患者的结局，这些患者使用了国际随机干扰素与 STI571 研究（IRIS）、评估尼洛替尼疗效和安全性的临床试验-新诊断患者（ENEST-nd）、达沙替尼与伊马替尼治疗初治 CML 患者（DASISION）和 MD 安德森癌症中心（MDACC）试验中使用的 PFS 和 EFS 定义。EFS-IRIS、ENEST-nd 中无进展时间、PFS-DASISION 和 EFS-MDACC 的定义如前所述。EFS-MDACC 认为任何原因导致的任何毒性或死亡均为事件（如果在死亡前不作为进展/事件计算）。
435 例患者中，123 例（28%）停止 TKI 治疗（耐药/无反应，n=33；TKI 治疗期间发生急变期，n=6；不耐受/毒性，n=29；其他原因，n=55）。33 例患者（7.6%）死亡；8 例死亡于 TKI 治疗期间，2 例死亡于 TKI 停药后 60 天内，23 例死亡于 TKI 停药后 60 天以上。在 33 例死亡中，19 例死亡（8 例死于 TKI，2 例死于 60 天内，9 例死于耐药/复发/转化）将计入 IRIS/ENEST-nd/DASISION 研究的进展/事件，而 14 例死亡将在 TKI 停药时被删失。根据 IRIS、ENEST-nd、DASISION 和 MDACC 试验使用的四个定义，相应的 5 年 PFS/EFS 率分别为 96%、90%、89%和 81%。
需要统一的 PFS 和 EFS 定义来比较 CML 中不同 TKI 的长期疗效和潜在用途。
