Singapore General Hospital, Duke-NUS Medical School, 20 College Road, Singapore, 169856, Singapore.
National University Cancer Institute, Singapore, Singapore.
Int J Hematol. 2021 Jul;114(1):65-78. doi: 10.1007/s12185-021-03144-4. Epub 2021 Apr 13.
Bosutinib is approved in the United States, Europe, Japan, and other countries for treatment of newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML), and CML resistant/intolerant to prior therapy. In the phase 3 BFORE trial (Clinicaltrials.gov, NCT02130557), patients were randomized 1:1 to first-line bosutinib or imatinib 400 mg once daily. We examined efficacy, safety, and patient-reported outcomes of bosutinib vs imatinib and pharmacokinetics of bosutinib in the Asian (n = 33 vs 34) and non-Asian (n = 235 vs 234) subpopulations of BFORE followed for at least 24 months. At the data cutoff date, 72.7 vs 66.7% of Asian and 70.6 vs 66.4% of non-Asian patients remained on treatment. The major molecular response rate at 24 months favored bosutinib vs imatinib among Asian (63.6 vs 38.2%) and non-Asian (60.9 vs 52.6%) patients, as did the complete cytogenetic response rate by 24 months (86.7 vs 76.7%, 81.5 vs 76.3%). Treatment-emergent adverse events in both subpopulations were consistent with the primary BFORE results. Trough bosutinib concentration levels tended to be higher in Asian patients. Health-related quality of life was maintained after 12 months of bosutinib in both subpopulations. These results support bosutinib as a first-line treatment option in Asian patients with CP CML.
博舒替尼已在美国、欧洲、日本和其他国家获批用于治疗新诊断的慢性期(CP)慢性髓性白血病(CML)以及对既往治疗耐药/不耐受的 CML。在 3 期 BFORE 试验(Clinicaltrials.gov,NCT02130557)中,患者按 1:1 随机分组,分别接受一线博舒替尼或伊马替尼 400mg 每日 1 次治疗。我们在 BFORE 中至少随访 24 个月的亚洲(n=33 与 n=34)和非亚洲(n=235 与 n=234)亚组中评估了博舒替尼对比伊马替尼的疗效、安全性和患者报告结局以及博舒替尼的药代动力学。截止数据分析日期,亚洲患者中分别有 72.7%和 66.7%、非亚洲患者中分别有 70.6%和 66.4%仍在接受治疗。亚洲患者和非亚洲患者在 24 个月时主要分子学反应率分别为博舒替尼优于伊马替尼(63.6%与 38.2%、60.9%与 52.6%),24 个月时完全细胞遗传学反应率也如此(86.7%与 76.7%、81.5%与 76.3%)。两个亚组的治疗中出现的不良事件与主要的 BFORE 结果一致。亚洲患者的博舒替尼谷浓度水平往往较高。在两个亚组中,博舒替尼治疗 12 个月后,健康相关生活质量得以维持。这些结果支持博舒替尼作为 CP CML 亚洲患者的一线治疗选择。