Bosutinib as third-line therapy for chronic phase (CP) chronic myeloid leukemia (CML) following failure with imatinib and dasatinib or nilotinib

SUMMARY: BOSULIF® (Bosutinib), an Abl and Src kinase inhibitor was approved by the FDA for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy. This trial included CML patients treated with imatinib followed by a second generation TKI. Five hundred and forty six (546) patients were enrolled in a single-arm, open-label, multi-center trial and these patients had either chronic phase (CP), accelerated phase (AP) or blast phase (BP) CML and were previously treated with at least one prior tyrosine kinase inhibitor (TKI). The primary endpoints for patients with CP CML were the rate of major cytogenetic response (MCyR) at week 24 and the duration of MCyR. The primary endpoints for patients with AP or BP CML were the rate of confirmed complete hematologic response (CHR) and overall hematologic response (OHR) by week 48. The MCyR at week 24 was 34% for those CP CML patients who received prior therapy with one TKI and 27% for those who received prior therapy with more than one TKI. The duration of MCyR among 53% of the patients who achieved MCyR at any time during the trial was 18 months, for patients with CP CML who had been treated with one prior TKI. For those CP CML patients treated with more than one TKI, the duration of MCyR among 51% of the patients who achieved MCyR at any time during the trial was 9 months. The CHR and OHR for AP CML who received at least one prior TKI were 30% and 55% respectively at week 48 whereas the BP CML group had a CHR and OHR of 15% and 28% respectively at week 48. BOSULIF® will be a welcome addition for those CML patients who had progressed on one or more tyrosine kinase inhibitors. Brummendorf TH, Cortes JE, Kantarjian H, et al. J Clin Oncol 29: 2011 (suppl; abstr 6535)