Uy Geoffrey L, Mandrekar Sumithra J, Laumann Kristina, Marcucci Guido, Zhao Weiqiang, Levis Mark J, Klepin Heidi D, Baer Maria R, Powell Bayard L, Westervelt Peter, DeAngelo Daniel J, Stock Wendy, Sanford Ben, Blum William G, Bloomfield Clara D, Stone Richard M, Larson Richard A
Washington University School of Medicine, St. Louis, MO.
Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN.
Blood Adv. 2017 Jan 24;1(5):331-340. doi: 10.1182/bloodadvances.2016003053.
The Cancer and Leukemia Group B (CALGB), now part of the Alliance for Clinical Trials in Oncology, conducted a multicenter, single-arm, phase 2 study in patients ≥60 years with FMS-like tyrosine kinase 3 ()-mutated acute myeloid leukemia (AML). In this study, sorafenib was added to daunorubicin and cytarabine-based induction and consolidation chemotherapy and was also continued for 12 months of maintenance therapy. The primary end point of the study was overall survival (OS) at 1 year in the FLT3 internal tandem duplication (FLT3-ITD) cohort. Fifty-four patients with a median age of 67 years (range, 60.3-82.7 years) were enrolled; 39 were -ITD patients (71%) and 15 were -TKD (29%) patients. The observed 1-year OS (95% confidence interval [CI]) was 62% (45%-78%) for the -ITD patients (meeting the primary end point 62% vs 30% for a historical control group, < .0001) and 71% (42%-92%) for the -TKD patients. The median disease-free survival and OS were 12.2 months (95% CI, 5-16.9) and 15.0 months (95% CI, 10.4-20.1), respectively, in the -ITD group and 9.6 (95% CI, 1.9 to not available [NA]) and 16.2 months (95% CI, 5.0 to NA) for the -TKD group. This study suggests that the addition of sorafenib to chemotherapy for -ITD AML is feasible and may improve the survival of older adults with -mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT01253070.
癌症与白血病B组（CALGB，现为肿瘤学临床试验联盟的一部分）针对年龄≥60岁、伴有FMS样酪氨酸激酶3（FLT3）突变的急性髓系白血病（AML）患者开展了一项多中心、单臂、2期研究。在本研究中，索拉非尼被添加到柔红霉素和阿糖胞苷为基础的诱导和巩固化疗方案中，并且维持治疗持续12个月。该研究的主要终点是FLT3内部串联重复（FLT3-ITD）队列患者1年的总生存期（OS）。共入组了54例患者，中位年龄为67岁（范围60.3 - 82.7岁）；其中39例为FLT3-ITD患者（71%），15例为FLT3-酪氨酸激酶结构域（TKD）突变患者（29%）。FLT3-ITD患者观察到的1年总生存期（95%置信区间[CI]）为62%（45% - 78%）（达到主要终点，与历史对照组的30%相比，P <.0001），FLT3-TKD患者为71%（42% - 92%）。FLT3-ITD组的中位无病生存期和总生存期分别为12.2个月（95% CI，5 - 16.9）和15.0个月（95% CI，10.4 - 20.1），FLT3-TKD组分别为9.6个月（95% CI，1.9至不可用[NA]）和16.2个月（95% CI，5.0至NA）。本研究表明，对于FLT3-ITD AML患者，在化疗中添加索拉非尼是可行的，并且可能改善老年FLT3突变AML患者的生存期。该试验在www.clinicaltrials.gov上注册，注册号为#NCT01253070。
