Takahashi Naoto, Nakaseko Chiaki, Kobayashi Yukio, Miyamura Koichi, Ono Chiho, Koide Yuichiro, Fujii Yosuke, Ohnishi Kazunori
Department of Hematology, Akita University Hospital, 1-1-1 Hondo, Akita, 010-8543, Japan.
Department of Hematology, Chiba University Hospital, Chiba, Japan.
Int J Hematol. 2017 Sep;106(3):398-410. doi: 10.1007/s12185-017-2239-8. Epub 2017 Apr 13.
This long-term follow-up of a completed phase 1/2 study assessed the safety and efficacy of bosutinib in Japanese Philadelphia chromosome-positive, chronic phase (CP) or advanced phase (ADV) chronic myeloid leukemia patients who were resistant/refractory or intolerant to prior tyrosine kinase inhibitor treatment. This analysis included 63 patients with a median bosutinib follow-up of 132 weeks (range 3‒372). In the CP second-line (2L) cohort, the cumulative major cytogenetic response (MCyR) and major molecular response (MMR) rates throughout the study were 73 and 53%, respectively. In the CP third-line (3L) cohort, the cumulative MCyR and MMR rates throughout the study were 70 and 40%, respectively. Of the eight ADV patients, MCyR was attained or maintained by 50% of patients, and complete hematologic response was attained or maintained by 25% of patients. Progression-free survival rate and overall survival rate at 96 weeks were, respectively, 91 and 98% in CP2L, 88 and 100% in CP3L, and 33 and 50% in ADV patients. The most common adverse events (>50%) reported were diarrhea (95%), nasopharyngitis (57%), and rash (57%). Bosutinib demonstrated durable efficacy and a manageable tolerability profile over long-term use in Japanese patients.ClinicalTrials.gov: NCT00811070.
这项对一项已完成的1/2期研究的长期随访评估了波舒替尼对日本费城染色体阳性、慢性期(CP)或进展期(ADV)慢性髓性白血病患者的安全性和疗效,这些患者对先前的酪氨酸激酶抑制剂治疗耐药/难治或不耐受。该分析纳入了63例患者,波舒替尼的中位随访时间为132周(范围3 - 372周)。在CP二线(2L)队列中,整个研究期间累积的主要细胞遗传学反应(MCyR)率和主要分子反应(MMR)率分别为73%和53%。在CP三线(3L)队列中,整个研究期间累积的MCyR率和MMR率分别为70%和40%。在8例ADV患者中,50%的患者达到或维持了MCyR,25%的患者达到或维持了完全血液学反应。CP2L患者96周时的无进展生存率和总生存率分别为91%和98%,CP3L患者分别为88%和100%,ADV患者分别为33%和50%。报告的最常见不良事件(>50%)为腹泻(95%)、鼻咽炎(57%)和皮疹(57%)。波舒替尼在日本患者长期使用中显示出持久的疗效和可管理的耐受性。ClinicalTrials.gov:NCT00811070。