Ingress Health, Rotterdam, The Netherlands.
Pfizer Inc., Groton, CT, USA.
Curr Med Res Opin. 2021 May;37(5):801-809. doi: 10.1080/03007995.2021.1896489. Epub 2021 Apr 2.
Bosutinib, nilotinib and dasatinib are approved for the treatment of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). In the absence of head-to-head comparisons between second-generation tyrosine kinase inhibitors (TKIs), the objective of this study was to indirectly compare the efficacy of bosutinib with nilotinib and dasatinib in first-line (1L) CP-CML.
Cross-trial heterogeneity in terms of patient baseline characteristics and imatinib dose escalation are difficult to adjust for in network meta-analyses and anchored matching-adjusted indirect treatment comparisons (MAICs). Therefore, an unanchored MAIC was performed using patient level data from bosutinib (BFORE trial) and published aggregated data from nilotinib (ENESTnd) and dasatinib (DASISION) trials. After matching, cytogenetic and molecular responses, and disease progression, after a minimum follow-up of 24 months were compared between nilotinib versus bosutinb and dasatinib versus bosutinib.
The comparison of nilotinib versus bosutinib resulted in no statistically significant differences for MMR at and by 24 months, MR4 by 24 months, MR4.5 at and by 24 months, CCyR by 24 months, and disease progression, however, a decreased odds of MR4 at 24 months in favor of bosutinib versus nilotinib was observed. The comparison of dasatinib versus bosutinib by 24 months resulted in no statistically significant differences for MMR, disease progression, and CCyR, however a decreased odds of MR4.5 in favor of bosutinib versus dasatinib was observed.
Overall, in these analyses bosutinib demonstrates equivalent efficacy to nilotinib and dasatinib in the treatment of patients with newly diagnosed CP-CML.
博舒替尼、尼洛替尼和达沙替尼获批用于治疗新诊断的慢性期慢性髓性白血病(CP-CML)患者。由于二代酪氨酸激酶抑制剂(TKI)之间没有头对头比较,因此本研究旨在间接比较博舒替尼与尼洛替尼和达沙替尼在一线(1L)CP-CML 中的疗效。
网络荟萃分析和锚定匹配调整间接治疗比较(MAIC)很难调整患者基线特征和伊马替尼剂量升级方面的交叉试验异质性。因此,使用博舒替尼(BFORE 试验)的患者水平数据和尼洛替尼(ENESTnd)和达沙替尼(DASISION)试验的已发表汇总数据进行了无锚 MAIC。匹配后,比较尼洛替尼与博舒替尼和达沙替尼与博舒替尼治疗 24 个月后最低随访时间的细胞遗传学和分子反应以及疾病进展。
尼洛替尼与博舒替尼的比较在 24 个月时和 24 个月时的主要分子反应(MMR)、24 个月时的 MR4、24 个月时的 MR4.5、24 个月时的 CCyR 以及疾病进展方面没有统计学上的显著差异,但观察到 24 个月时博舒替尼对比尼洛替尼 MR4 的优势比降低。达沙替尼与博舒替尼的比较在 24 个月时的 MMR、疾病进展和 CCyR 方面没有统计学上的显著差异,但观察到 24 个月时博舒替尼对比达沙替尼 MR4.5 的优势比降低。
总体而言,在这些分析中,博舒替尼在治疗新诊断的 CP-CML 患者方面显示出与尼洛替尼和达沙替尼相当的疗效。