First-line tyrosine kinase inhibitors: Comparing bosutinib and imatinib

This study compared the effectiveness of two types of tyrosine kinase inhibitors – imatinib (Gleevac) and bosutinib (Bosulif) – for chronic myeloid leukemia (CML). Researchers reported higher treatment response rates with bosutinib than with imatinib. 

 Many patients with CML have an abnormally short chromosome (structure at the nucleus of most living cells that carry genetic information) called the Philadelphia chromosome. This chromosome carries a gene abnormality called BCR-ABL, which plays a role in the process that creates abnormal white blood cells characteristic of CML.

Patients treated for CML who are no longer showing any cells with the Philadelphia chromosome in their blood or bone marrow are considered to have reached complete cytogenetic response (CCR). An even stronger response to treatment is molecular response, when the amount of BCR-ABL gene in the blood is low or untraceable. Major molecular response (MMR) is typically the ultimate goal of CML treatment.

Tyrosine kinase inhibitors are a type of targeted therapy that block enzymes called tyrosine kinases and are a first-line treatment for CML. Imatinib is the most commonly used tyrosine kinase inhibitor. However, it has been suggested that second-generation tyrosine kinase inhibitors, such as bosutinib, could be more effective. 

The aim of this study was to compare bosutinib and imatinib as first-line therapies for CML.

536 patients with chronic (early) phase CML who were positive for the Philadelphia chromosome were included in this study. Patients were randomly assigned to either receive treatment with imatinib or with bosutinib (at 400 mg per day). Treatment response rates at 12 months were compared between groups.

MMR rates at 12 months were significantly higher for patients treated with bosutinib (47.2%) than those treated with imatinib (36.9%). MMR rates were higher with bosutinib for patients with low, intermediate, and high risk disease.

CCR rates at 12 months were also significantly higher for patients receiving bosutinib (77.2%) versus imatinib (66.4%). Overall, patients treated with bosutinib were 38% more likely to achieve CCR compared to imatinib.

4 patients (1.6%) receiving bosutinib and 6 patients (2.5%) receiving imatinib experienced disease progression during the treatment period. 7 patients died during the study period. Of these, 6 were treated with imatinib and 1 with bosutinib.

12.7% of patients receiving bosutinib and 8.7% of patients receiving imatinib stopped treatment due to side effects. Common side effects included diarrhea, reduced liver function, nausea, and low white blood cell counts. Reduced liver function was observed in patients treated with bosutinib. The imatinib group was more likely to experience muscle spasms. 

Researchers reported superior treatment response rates with bosutinib than with imatinib.

This study was sponsored by Avillion and Pfizer, the manufacturers of bosutinib.