Bosulif

Drug Overview

Bosulif (bosutinib; Pfizer) is a kinase inhibitor that targets the BCR-ABL kinase and also inhibits the Src-family kinases that include Src, Lyn, and Hck. The BCR-ABL kinase is upregulated in the presence of an abnormal BCR-ABL fusion protein, which is a common hallmark of chronic myeloid leukemia (CML). Overexpression of specific Src kinases is associated with Gleevec-resistant CML phenotypes. In mice, treatment with Bosulif reduced the size of CML tumors relative to controls and inhibited growth of murine myeloid tumors expressing several Gleevec-resistant forms of BCR-ABL.

Bosulif was the fourth tyrosine kinase inhibitor (TKI) to enter the CML market and is most commonly used in the third-line setting. Bosulif benefits from its activity against CML mutations that confer resistance to Gleevec (imatinib; Novartis), Sprycel (dasatinib; Bristol-Myers Squibb/Otsuka), and Tasigna (nilotinib; Novartis). The drug failed to demonstrate a statistically significant difference in cytogenetic response versus Gleevec in the Phase III BELA trial; however, Pfizer is making a second attempt in first-line CML with the Phase III BFORE trial. Nonetheless, Bosulif’s late entry into the CML market will continue to hinder its uptake.