Cortes Jorge E, Saglio Giuseppe, Kantarjian Hagop M, Baccarani Michele, Mayer Jiří, Boqué Concepción, Shah Neil P, Chuah Charles, Casanova Luis, Bradley-Garelik Brigid, Manos George, Hochhaus Andreas
Jorge E. Cortes and Hagop M. Kantarjian The University of Texas MD Anderson Cancer Center, Houston, TX; Neil P. Shah, University of California San Francisco School of Medicine, San Francisco, CA; Brigid Bradley-Garelik and George Manos, Bristol-Myers Squibb, Princeton, NJ; Giuseppe Saglio, University of Turin, Turin; Michele Baccarani, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; Jiří Mayer, University Hospital Brno and Central European Institute of Technology, Masaryk University, Brno, Czech Republic; Concepción Boqué, Institut Català d'Oncologia, Hospital Duran i Reynals, L'Hospitalet, Barcelona, Spain; Charles Chuah, Singapore General Hospital, Duke-National University of Singapore Medical School, Singapore; Luis Casanova, Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú;and Andreas Hochhaus, Universitätsklinikum Jena, Jena, Germany.
J Clin Oncol. 2016 Jul 10;34(20):2333-40. doi: 10.1200/JCO.2015.64.8899. Epub 2016 May 23.
We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib.
Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260).
At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5% and 7% of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1. Arterial ischemic events were uncommon in both treatment arms.
These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long-term treatment of CML-CP.
我们报告了初治慢性髓性白血病患者达沙替尼与伊马替尼研究（DASISION）III期试验的5年分析结果，评估了接受达沙替尼或伊马替尼治疗的慢性期（CP）慢性髓性白血病（CML）患者的长期疗效和安全性结局。
新诊断的CML-CP患者被随机分配接受每日一次100 mg达沙替尼治疗（n = 259）或每日一次400 mg伊马替尼治疗（n = 260）。
在研究结束时，接受达沙替尼和伊马替尼治疗的患者分别有61%和63%仍在接受初始治疗。与伊马替尼相比，达沙替尼治疗的患者在5年时主要分子反应以及BCR-ABL1转录本较基线降低4.0或4.5个对数的分子反应的累积发生率在统计学上仍显著更高。两个治疗组5年时的无进展生存率和总生存率均保持在较高水平且相似。在3个月时BCR-ABL1≤10%的患者中（达沙替尼组为84%，伊马替尼组为64%），与3个月时BCR-ABL1大于10%的患者相比，报告的无进展生存率和总生存率有所改善，且加速期/急变期转化率较低。达沙替尼组和伊马替尼组分别有5%和7%的患者转化为加速期/急变期。15例接受达沙替尼治疗和19例接受伊马替尼治疗的患者在停药时检测到BCR-ABL1突变。两个治疗组均未发现新的或意外的不良事件，胸腔积液是唯一与药物相关且达沙替尼组报告更频繁的非血液学不良事件（28%对比伊马替尼组的0.8%）。达沙替尼组报告了胸腔积液的首次发生情况，第1年发病率最高。两个治疗组动脉缺血事件均不常见。
DASISION试验的这些最终结果继续支持每日一次100 mg达沙替尼作为CML-CP长期治疗的安全有效一线疗法。
