Author(s): Cortes JE, Kantarjian HM, Brmmendorf TH, Kim DW, Turkina AG,
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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.
This article was published in Blood
and referenced in Journal of Carcinogenesis & Mutagenesis