Leukemia Drug Bosulif Succeeds in Phase 3 Trial

Treatment is superior to imatinib in adults with CML

Positive results have been reported from a phase 3 comparison of bosutinib (Bosulif, Pfizer/Avillion) and imatinib as first-line treatments in patients with chronic-phase Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML). The study met its primary endpoint of a superior major molecular response (MMR) at 12 months with bosutinib compared with imatinib. Bosutinib is currently indicated in the U.S. for the treatment of adults with Ph+ CML who were resistant to or intolerant of prior therapy.

The Bosutinib Trial in First-Line ChrOnic Myelogenous Leukemia TREatment (BFORE) was an open-label study designed to assess the efficacy and safety of bosutinib as first-line treatment for adults with chronic phase Ph+ CML. The study enrolled 536 patients at sites in North America, Asia, and Europe. The patients were randomly assigned to receive bosutinib (400 mg) or imatinib, a standard of care, for the duration of the study. The primary objective was to demonstrate the superiority of bosutinib over imatinib at 12 months by comparing MMRs, or the proportion of patients in each treatment arm whose levels of Bcr-Abl1 kinase had dropped to below 0.1%.

Bosutinib is an oral, once-daily tyrosine kinase inhibitor (TKI) that inhibits the Bcr-Abl kinase, which promotes CML; it is also an inhibitor of Src-family kinases. Bosutinib was approved by the FDA in September 2012 for the treatment of adults with Ph+ CML who were resistant to or intolerant of prior therapy. The current approved dosage of bosutinib is 500 mg once daily with food.

Pfizer and Avillion entered into a collaborative development agreement in 2014 to conduct the BEFORE trial. Under the terms of the agreement, Avillion provided funding and conducted the study to generate the clinical data that will be used to support regulatory filings for marketing authorization of bosutinib as a first-line treatment for patients with chronic-phase Ph+ CML. Pfizer has retained all rights to commercialize bosutinib globally.

Source: Pfizer; December 5, 2016.