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
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Bosutinib active in patients with Philadelphia chromosome–positive (Ph+) leukemia and with resistance or intolerance to second-generation tyrosine kinase inhibitors (TKIs)
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Activity noted across baseline Bcr-Abl kinase domain mutations conferring clinical resistance to dasatinib (F317L) and nilotinib (Y253H, E255K/V, and F359C/V)
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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
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Baseline mutations associated with diminished response to bosutinib in patients with advanced leukemia
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At completion of bosutinib treatment, new mutations identified in 27% of patients
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Most common emergent mutations: T315I and V299L
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Emergent mutations more common in patients with preexisting mutations
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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
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
