Benefits and risks of ponatinib versus bosutinib following treatment failure of two prior tyrosine kinase inhibitors in patients with chronic phase chronic myeloid leukemia: a matching-adjusted indirect comparison

Abstract

Objective: Comparing the benefit–risk profiles of ponatinib vs. bosutinib in third-line (3L) treatment of chronic phase chronic myeloid leukemia (CP-CML) is challenging because their pivotal trials lacked comparator arms. To characterize the overall benefit–risk profile in 3L CP-CML patients treated with bosutinib vs. ponatinib, a matching-adjusted indirect comparison (MAIC) was performed to compare efficacy outcomes and treatment duration after adjusting for trial subjects’ baseline characteristics, and tolerability was assessed with an unadjusted comparison of study-drug discontinuation.

Methods: The MAIC was performed using published data from the pivotal bosutinib trial and the most recent individual-patient-level data on file from the pivotal ponatinib trial.

Results: Responses were more frequent and durable with ponatinib (n = 70 MAIC-adjusted) than with bosutinib (n = 119) – complete cytogenetic response (CCyR): 61% vs. 26%; Kaplan–Meier estimate of maintaining CCyR at 4 years: 89% vs. 54%. Median treatment duration was longer with ponatinib than with bosutinib: 38.4 vs. 8.6 months. Only 9% of ponatinib patients (n = 97 unadjusted) vs. 42% of bosutinib patients discontinued due to death, disease progression or unsatisfactory response; 19% vs. 24% discontinued due to adverse events.

Conclusions: Based on these surrogate measures of patient benefit–risk profiles, ponatinib appears to provide a net overall benefit vs. bosutinib in 3L CP-CML.

Keywords:

• Indirect comparison
• ponatinib
• bosutinib
• tyrosine kinase inhibitor
• chronic myeloid leukemia
• chronic myelogenous leukemia

Transparency

Declaration of funding

This study and preparation of this article were funded by Ariad Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Author contributions

M.Y.L., L.J.M., H.H., S.C. and S.I. contributed to study conception. L.J.M. and S.I. contributed to study design. M.Y.L., L.J.M., S.L. and S.I. contributed to data analysis. M.Y.L., L.J.M., S.L., S.C. and S.I. contributed to data interpretation. All authors participated in manuscript drafting and/or revision, approved the final manuscript for publication, and agree to be held accountable for all aspects of the work.

Declaration of financial/other relationships

M.Y.L. has disclosed that he has received advisory board and speaking fees from Takeda, Abbvie, Genentech and Johnson & Johnson. L.J.M. and S.C. have disclosed that they were employees of Ariad when this research was conducted, and held stocks/options in Ariad. H.H. and S.L. have disclosed that they are employees of Ariad/Takeda, and hold stocks/options in Ariad. S.I. has disclosed that he has received consulting fees and research support from Ariad Pharmaceuticals Inc. and Incyte Biosciences Sàrl.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The MAIC analyses were supported by Ariad Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, through a consulting contract with SIHS SRL, a company owned and directed by S.I. Editorial assistance in the preparation of this manuscript was provided by W. Mark Roberts PhD, Montreal, Canada, and was funded by Ariad Pharmaceuticals Inc.