Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome–positive CML patients with resistance or intolerance to imatinib

Jorge E. Cortes, Hagop M. Kantarjian, Tim H. Brümmendorf, Dong-Wook Kim, Anna G. Turkina, Zhi-Xiang Shen, Ricardo Pasquini, H. Jean Khoury, Steven Arkin, Angela Volkert, Nadine Besson, Richat Abbas, Junyuan Wang, Eric Leip and Carlo Gambacorti-Passerini
This article has an Erratum 122(14):2524


Bosutinib, a dual Src/Abl kinase inhibitor, has shown potent activity against chronic myeloid leukemia (CML). This phase I/II study evaluated bosutinib in patients with chronic phase imatinib-resistant or imatinib-intolerant CML. Part 1 was a dose-escalation study to determine the recommended starting dose for part 2; part 2 evaluated efficacy and safety of bosutinib 500 mg once-daily dosing. The study enrolled 288 patients with imatinib-resistant (n = 200) or imatinib-intolerant (n = 88) CML and no other prior kinase inhibitor exposure. At 24 weeks, 31% of patients achieved major cytogenetic response (MCyR; primary endpoint). After a median follow-up of 24.2 months, 86% of patients achieved complete hematologic remission, 53% had a MCyR (41% had a complete cytogenetic response [CCyR]), and 64% of those achieving CCyR had a major molecular response. At 2 years, progression-free survival was 79%; overall survival at 2 years was 92%. Responses were seen across Bcr-Abl mutants, except T315I. Bosutinib exhibited an acceptable safety profile; the most common treatment-emergent AE was mild/moderate, typically self-limiting diarrhea. Grade 3/4 non-hematologic AEs (>2% of patients) included diarrhea (9%), rash (9%), and vomiting (3%). These data suggest bosutinib is effective and tolerable in patients with chronic phase imatinib-resistant or imatinib-intolerant CML. This trial was registered at as #NCT00261846.

  • Submitted May 25, 2011.
  • Accepted August 10, 2011.