Chen Kang-Kang, Du Tai-Feng, Wu Ku-Sheng, Yang Wei
Department of Preventive Medicine and MPH Education Center, Shantou University Medical College, Shantou, Guangdong Province, China.
Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong Province, China.
Cancer Manag Res. 2018 Sep 25;10:3891-3910. doi: 10.2147/CMAR.S177566. eCollection 2018.
With bosutinib proven to be available for frontline treatment, there are currently four frontline treatments as well as an additional strategy with high-dose imatinib for newly diagnosed chronic myeloid leukemia (CML). Due to the lack of direct comparison of high-dose imatinib, dasatinib, nilotinib, and bosutinib, we summarized the evidence to indirectly compare the efficacy among these treatment options.
In total, 14 randomized clinical trials including 5,630 patients were analyzed by direct and mixed-treatment comparisons. Outcomes assessed were the following: complete cytogenetic response at 12 months; major molecular response at 12, 24, and 36 months; deep molecular response at 12, 24, 36, and 60 months; early molecular response at 3 months; progression-free survival (PFS); overall survival (OS); and Grade 3 or 4 adverse events (AEs).
The Bayesian network meta-analysis demonstrated that high-dose imatinib was less effective than all new-generation tyrosine kinase inhibitors and had a higher probability of Grade 3 or 4 AEs. For molecular response, 300 mg of nilotinib was likely to be the preferred frontline treatment, as demonstrated by higher response rates and faster, deeper, and longer molecular response. For PFS and OS, there were high likelihoods (79% and 74%, respectively) that 400 mg of nilotinib was the preferred option. For AEs, standard-dose imatinib has the highest probability (65%) of being the most favorable toxicity profile.
Considering the efficacy and toxicity profile, it is not recommended to use high-dose imatinib for treatment. This analysis also showed that nilotinib has the highest probability to become the preferred frontline agents for treating CML.
鉴于波舒替尼已被证明可用于一线治疗，目前新诊断的慢性髓性白血病（CML）有四种一线治疗方法以及一种高剂量伊马替尼的额外策略。由于缺乏高剂量伊马替尼、达沙替尼、尼洛替尼和波舒替尼的直接比较，我们总结了证据以间接比较这些治疗方案的疗效。
通过直接和混合治疗比较分析了总共14项随机临床试验，包括5630名患者。评估的结果如下：12个月时的完全细胞遗传学反应；12、24和36个月时的主要分子反应；12、24、36和60个月时的深度分子反应；3个月时的早期分子反应；无进展生存期（PFS）；总生存期（OS）；以及3级或4级不良事件（AE）。
贝叶斯网络荟萃分析表明，高剂量伊马替尼的疗效低于所有新一代酪氨酸激酶抑制剂，且发生3级或4级AE的概率更高。对于分子反应，300mg尼洛替尼可能是首选的一线治疗方法，更高的反应率以及更快、更深和更长时间的分子反应证明了这一点。对于PFS和OS，400mg尼洛替尼极有可能（分别为79%和74%）是首选方案。对于AE，标准剂量伊马替尼具有最有利毒性特征的概率最高（65%）。
考虑到疗效和毒性特征，不建议使用高剂量伊马替尼进行治疗。该分析还表明，尼洛替尼最有可能成为治疗CML的首选一线药物。
