With no head-to-head trials comparing bosutinib with ponatinib, a matching-adjusted indirect comparison concluded that ponatinib offers better disease control than bosutinib in patients who are intolerant to or have progressed on prior tyrosine kinase inhibitor (TKI) therapy.
Ponatinib was found to provide better clinical responses than bosutinib in the third-line treatment of patients with chronic phase (CP) chronic myeloid leukemia (CML) in a matching-adjusted indirect comparison (MAIC).1
Major cytogenetic responses (MCyR) and complete cytogenetic responses (CCyR) with ponatinib were greater than twice the response rates seen with bosutinib. The results were published online in Current Medical Research and Opinion.1
Ponatinib Compared With Bosutinib
In the United States, ponatinib and bosutinib received initial approvals for the treatment of patients with Philadelphia chromosome-positive (Ph+) CML who are intolerant to or have progressed on prior TKI therapy.
Bosutinib was approved based on data from a phase 1/2 study in patients with CML who were resistant or intolerant to imatinib and had failed subsequent therapy on nilotinib or dasatinib.2Ponatinib received a similar approval based on data from the phase 2 PACE study.3
With no head-to-head trials comparing the two agents, an optimal choice of therapy for the third-line treatment of patients with CML was not possible. A MAIC analysis provides a rationale for this comparison.
The MAIC analysis allowed the investigators to extract data from the initial studies and long-term follow up studies from the bosutinib studies and compared them with patient-level data from PACE available to the investigators. Individual patients treated with ponatinib were assigned weights such that the weighted mean baseline characteristics in PACE exactly matched the baseline characteristics for patients treated with bosutinib.1
These weights were applied to provide matching-adjusted response rates and duration of responses.
More than twice as many patients achieved a MCyR with ponatinib (69.8% vs 33.0% for bosutinib). Similar observations were made for CCyR (61.2% vs 25.9% for bosutinib). Of patients who achieved a CCyR, 42% and 3% of patients on bosutinib and ponatinib, respectively, lost the response within the first year.1
At 4 years, it was estimated that 54% of patients on bostunib and 89% of patients on ponatinib maintained the initial CCyR. Also, twice as many patients remained on treatment with ponatinib at 4 years — 48% vs 24% for bosutinib.1
Overall survival at this time point similar (78% for bosutinib and 83% for ponatinib) as was median progression-free survival (76% for bosutinib and 69% for ponatinib).1
Based on initial observations (unadjusted) from the respective registration studies, treatment failure — defined as death, disease progression, or lack of efficac y — was more than 4-fold higher for patients administered bosutinib (42% vs 9% for ponatinib).