Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia
Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia
复制标题
DOI：
10.1056/nejmoa1002315
复制
发表时间：
2010-06-17
影响因子：
158.5
通讯作者：
Baccarani, Michele
中科院分区：
文献类型：
--
作者：
Kantarjian, Hagop;Shah, Neil P.;Baccarani, Michele
达沙替尼是一种高效的BCR-ABL激酶抑制剂，在伊马替尼治疗失败的慢性期慢性粒细胞白血病（CML）患者中，达沙替尼治疗导致了高比率的完全细胞遗传学缓解和无进展生存。我们评估了达沙替尼的疗效和安全性，与伊马替尼相比，为一线治疗慢性期CML。MethodsIn一项多国研究中，519例新诊断的慢性期CML患者被随机分配接受达沙替尼剂量为100毫克，每天一次（259例）或伊马替尼剂量为400毫克，每天一次（260例）。主要终点是12个月时的完全细胞遗传学缓解，在至少间隔28天的两次连续评估中得到证实。次要终点（包括主要分子反应）在0.0001的显著性水平下进行测试，以调整多重比较。结果经过至少12个月的随访后，达沙替尼组确认的完全细胞遗传学缓解率高于伊马替尼组（77% vs. 66%，P = 0.007），在至少一次评估中观察到的完全细胞遗传学缓解率也是如此（83% vs. 72%，P = 0.001）。达沙替尼组的主要分子学缓解率高于伊马替尼组（46% vs. 28%，P
BackgroundTreatment with dasatinib, a highly potent BCR-ABL kinase inhibitor, has resulted in high rates of complete cytogenetic response and progression-free survival among patients with chronic myeloid leukemia (CML) in the chronic phase, after failure of imatinib treatment. We assessed the efficacy and safety of dasatinib, as compared with imatinib, for the first-line treatment of chronic-phase CML.MethodsIn a multinational study, 519 patients with newly diagnosed chronic-phase CML were randomly assigned to receive dasatinib at a dose of 100 mg once daily (259 patients) or imatinib at a dose of 400 mg once daily (260 patients). The primary end point was complete cytogenetic response by 12 months, confirmed on two consecutive assessments at least 28 days apart. Secondary end points, including major molecular response, were tested at a significance level of 0.0001 to adjust for multiple comparisons.ResultsAfter a minimum follow-up of 12 months, the rate of confirmed complete cytogenetic response was higher with dasatinib than with imatinib (77% vs. 66%, P = 0.007), as was the rate of complete cytogenetic response observed on at least one assessment (83% vs. 72%, P = 0.001). The rate of major molecular response was higher with dasatinib than with imatinib (46% vs. 28%, P