OBJECTIVE:

To review clinical trials and main characteristics of bosutinib, a second-generation tyrosine kinase inhibitor (TKI) for treatment of chronic myelogenous leukemia (CML).

DATA SOURCES:

Pertinent data were identified through a search of PubMed (January 1990-April 2013) using the primary search terms SKI-606, bosutinib, and CML. Additionally, preliminary reports published in abstract form by the American Society of Clinical Oncology and American Society of Hematology (January 1990-April 2013) were screened for inclusion.

STUDY SELECTION AND DATA EXTRACTION:

Clinical Phase 1, 2, and 3 studies reported in English evaluating the safety and efficacy of bosutinib in patients with CML were reviewed.

DATA SYNTHESIS:

Bosutinib is a TKI of the breakpoint cluster region/Abelson murine leukemia (BCR-ABL) gene approved by the Food and Drug Administration on September 4, 2012, for second-line treatment of chronic phase, accelerated phase, and blast phase CML. In the second-line setting, bosutinib is effective in some patients with CML resistant or intolerant to imatinib, dasatinib, and/or nilotinib, but it is not effective in patients whose disease expresses the T315I point mutation in BCR-ABL. Bosutinib also has been compared with imatinib, the standard first-line treatment, in 502 patients with newly diagnosed chronic phase CML in a Phase 3 trial. Complete cytogenetic response at 12 months, the primary efficacy end point, is similar between bosutinib and imatinib (p = 0.601); therefore, bosutinib is not indicated in the first-line setting. Common adverse events associated with bosutinib include diarrhea, nausea, and vomiting. Grade 3 and 4 adverse events reported in at least 5% of bosutinib-treated patients include elevated serum lipase and liver aminotransferases, anemia, thrombocytopenia, neutropenia, and diarrhea.

CONCLUSIONS:

Currently available clinical trials suggest that bosutinib is generally a safe and effective treatment option for patients with CML who have failed first-line TKIs and who do not express the T315I mutation; however, tolerability may be problematic for some patients.