An indirect comparison between bosutinib, nilotinib and dasatinib in first-line chronic phase chronic myeloid leukemia

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusions

Overall, in these analyses bosutinib demonstrates equivalent efficacy to nilotinib and dasatinib in the treatment of patients with newly diagnosed CP-CML.

Keywords:

• Chronic myeloid leukemia
• first line
• bosutinib
• dasatinib
• nilotinib

Transparency

Declaration of funding

This study was sponsored by Pfizer. This publication reports the results of a Pfizer-sponsored non-interventional study.

Declaration of financial/other relationships

BM has disclosed that, at the time of this research, he was an employee of Ingress-health BV, which received financial support from Pfizer in connection with the conduct of this study and development of this manuscript. In his salaried position, he has worked with a variety of companies and organizations and was precluded from receiving payment or honoraria directly from these organizations for services rendered. BH has disclosed that he is an employee of Ingress-health BV and an equity holder of Ingress-health BV, which received financial support from Pfizer in connection with the conduct of this study and development of this manuscript. CM, JCC, EL and AV have disclosed that they are employees and shareholders of Pfizer Inc. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no other relevant financial relationships to disclose.

Author contributions

BM, CM, JCC, EL, AV, BH: conception, design, analysis and interpretation of the data, drafting of the paper and revising it critically for intellectual content. All authors agree to be accountable for all aspects of the work.

Acknowledgements

Not applicable.