比较尼洛替尼和达沙替尼在新诊断的慢性髓性白血病中的疗效：随机试验的匹配调整间接比较。

Comparative efficacy of nilotinib and dasatinib in newly diagnosed chronic myeloid leukemia: a matching-adjusted indirect comparison of randomized trials.

机构信息

Analysis Group , Boston, MA 02199, USA.

出版信息

Curr Med Res Opin. 2011 Jun;27(6):1263-71. doi: 10.1185/03007995.2011.576238. Epub 2011 Apr 28.

DOI:10.1185/03007995.2011.576238

PMID:21524239

Abstract

OBJECTIVE

Nilotinib and dasatinib have not been directly compared in a randomized trial for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP). The purpose of this study was to indirectly compare rates of major molecular response (MMR), progression-free survival (PFS) and overall survival by month 12 with nilotinib and dasatinib treatment of newly diagnosed CML-CP.

METHODS

Individual patient data from a randomized trial of nilotinib vs. imatinib (ENESTnd) and published summary data from a separate randomized trial of dasatinib vs. imatinib (DASISION) were utilized. A matching-adjusted indirect comparison was conducted by weighting individual patients treated with nilotinib to match baseline characteristics reported for dasatinib-treated patients, including age, gender, ECOG performance status and hematology lab values. After matching, efficacy outcomes were compared for patients treated with nilotinib 300 mg twice daily vs. dasatinib 100 mg once daily. Patients randomized to imatinib 400 mg once daily in each trial were used to assess the adequacy of the matching.

RESULTS

Before matching, patients randomized to nilotinib in ENESTnd (n = 273) were older, with a lower median platelet count and more favorable performance status compared to patients randomized to dasatinib in DASISION (n = 259). After matching, all baseline characteristics were balanced across treatment groups. Matched patients treated with nilotinib vs. dasatinib experienced significantly higher rates of MMR (56.8 vs. 45.9%, p = 0.014) and overall survival (99.5 vs. 97.3%, p = 0.046) and numerically higher rates of PFS (98.8 vs. 96.5%). Matched imatinib arms showed no statistically significant or clinically meaningful differences in these outcomes.

LIMITATIONS

Baseline measures unavailable in one or both trials could not be matched. Adverse event rates were not formally compared across trials due to differences in reporting.

CONCLUSION

Nilotinib was associated with significantly higher rates of MMR and overall survival compared with dasatinib by month 12 in the treatment of newly diagnosed CML-CP.

摘要

目的

尼洛替尼和达沙替尼尚未在治疗新诊断的慢性髓性白血病慢性期（CML-CP）的随机试验中进行直接比较。本研究的目的是通过尼洛替尼和达沙替尼治疗新诊断的 CML-CP 的 12 个月主要分子反应（MMR）、无进展生存期（PFS）和总生存期的间接比较率。

方法

利用一项尼洛替尼与伊马替尼（ENESTnd）的随机试验的个体患者数据和一项达沙替尼与伊马替尼（DASISION）的单独随机试验的已发表汇总数据。通过加权接受尼洛替尼治疗的个体患者，使其与达沙替尼治疗患者的报告基线特征相匹配（包括年龄、性别、ECOG 表现状态和血液学实验室值），进行匹配调整的间接比较。匹配后，比较接受尼洛替尼 300mg 每日两次与达沙替尼 100mg 每日一次治疗的患者的疗效结局。在每个试验中随机接受伊马替尼 400mg 每日一次的患者用于评估匹配的充分性。

结果

在匹配之前，ENESTnd 中随机接受尼洛替尼治疗的患者（n=273）年龄较大，血小板计数中位数较低，表现状态较好，而 DASISION 中随机接受达沙替尼治疗的患者（n=259）则年龄较小，血小板计数中位数较高，表现状态较差。匹配后，两组的所有基线特征均达到平衡。与接受达沙替尼治疗的患者相比，接受尼洛替尼治疗的匹配患者的 MMR（56.8%比 45.9%，p=0.014）和总生存期（99.5%比 97.3%，p=0.046）更高，PFS 也更高（98.8%比 96.5%）。在这些结局方面，匹配的伊马替尼组没有显示出统计学意义或临床意义上的差异。