Examining bosutinib as a treatment option for patients not responding to multiple first-line tyrosine kinase inhibitors

This study examined the effectiveness of bosutinib (Bosulif), a tyrosine kinase inhibitor (TKI), after previous treatment with multiple TKIs for chronic myeloid leukemia (CML). Researchers concluded that bosutinib was associated with good effectiveness for CML patients for whom previous TKIs have failed.

Targeted therapy is the standard first-line treatment for CML. This refers to a type of treatment that uses drugs or small molecules that block the growth and spread of cancer. TKIs are a type of targeted therapy that block enzymes called tyrosine kinases. Imatinib (Gleevac), nilotinib (Tasigna), and dasatinib (Sprycel) are TKIs that are commonly used to treat CML. Over time, however, some patients stop responding to first-line TKIs or have to discontinue treatment due to side effects. Based on early results, bosutinib may be used as a second-line TKI treatment. However, more studies are needed.

The aim of this study was to examine bosutinib as a treatment option for CML after previous treatment with multiple TKIs.

The study included 118 patients with chronic phase CML. All patients had been previously treated with imatinib followed by dasatinib and/or nilotinib. Previous TKI treatment either resulted in resistance or intolerance. All patients were then treated with bosutinib for an average of 8.3 months. Treatment outcomes were followed for an average of 28.5 months.

24% of patients achieved complete cytogenetic response (showing significantly reduced abnormal chromosomes in the blood or bone marrow). 32% of patients reached major cytogenetic response. One of 3 patients who were previously treated with all 3 first-line TKIs achieved complete cytogenetic response with bosutinib. 73% of patients achieved hematological response to bosutinib treatment (normalization of blood counts, particularly white blood cell counts).

5 patients experienced disease progression during the study period. At 2 years, 73% of patients were progression-free. The estimated overall survival rate (proportion who have not died from any cause since treatment) at 2 years was 83%.

The most common side effects associated with bosutinib included diarrhea (occurring in 81% of patients), nausea (43%), and vomiting (32%). Severe diarrhea was reported by 8% of patients and severe vomiting by 1% of patients. These side effects often occurred early during treatment (within 1.5 to 19.5 days) and were resolved in 80 to 94% of patients. Side effects affecting blood counts were uncommon and usually not serious.

Researchers concluded that bosutinib can provide an effective treatment option for some CML patients for whom multiple TKIs have failed.