Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia 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, Carlo Gambacorti-Passerini

Research output: Contribution to journalArticle

297 Scopus citations

Abstract

Bosutinib, a dual Src/Abl kinase inhibitor, has shown potent activity against chronic myeloid leukemia (CML). In this phase 1/2 study we 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 the 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 previous kinase inhibitor exposure. At 24 weeks, 31% of patients achieved major cytogenetic response (primary end point). After a median follow-up of 24.2 months, 86% of patients achieved complete hematologic remission, 53% had a major cytogenetic response (41% had a complete cytogenetic response), and 64% of those achieving complete cytogenetic response 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 adverse event was mild/moderate, typically self-limiting diarrhea. Grade 3/4 nonhematologic adverse events (> 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 http://www.clinicaltrials. gov as NCT00261846.

Original languageEnglish (US)
Pages (from-to)4567-4576
Number of pages10
JournalBlood
Volume118
Issue number17
DOIs
StatePublished - Oct 27 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Cortes, J. E., Kantarjian, H. M., Brümmendorf, T. H., Kim, D. W., Turkina, A. G., Shen, Z. X., Pasquini, R., Khoury, H. J., Arkin, S., Volkert, A., Besson, N., Abbas, R., Wang, J., Leip, E., & Gambacorti-Passerini, C. (2011). Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood, 118(17), 4567-4576. https://doi.org/10.1182/blood-2011-05-355594