Bosutinib Active in Patients With Philadelphia Chromosome–Positive Leukemia Resistant to Second-Generation TKIs Posting Date: December 13, 2011

Bosutinib Active in Patients With Philadelphia Chromosome–Positive Leukemia Resistant to Second-Generation TKIs

Posting Date: December 13, 2011

Nonrandomized, multicenter, open-label, phase I/II trial

Summary of Key Conclusions

• Bosutinib active in patients with Philadelphia chromosome–positive (Ph+) leukemia and with resistance or intolerance to second-generation tyrosine kinase inhibitors (TKIs)
• Activity noted across baseline Bcr-Abl kinase domain mutations conferring clinical resistance to dasatinib (F317L) and nilotinib (Y253H, E255K/V, and F359C/V)
• Limited activity in the presence of T315I mutation, which confers resistance to all TKIs Similar response to bosutinib across patients with chronic-phase chronic myeloid leukemia (CP CML), regardless of baseline resistance mutations
• Baseline mutations associated with diminished response to bosutinib in patients with advanced leukemia
• At completion of bosutinib treatment, new mutations identified in 27% of patients
• Most common emergent mutations: T315I and V299L
• Emergent mutations more common in patients with preexisting mutations
• Patients with emergent mutations more likely to discontinue treatment due to PD or unsatisfactory response to bosutinib

http://www.clinicaloptions.com/Oncology/Conference%20Coverage/Hematology%202011/Tracks/CML/Capsules/110.aspx