Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure.
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Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. / Khoury, H Jean; Cortes, Jorge E; Kantarjian, Hagop M; Gambacorti-Passerini, Carlo; Baccarani, Michele; Kim, Dong-Wook; Zaritskey, Andrey; Countouriotis, Athena; Besson, Nadine; Leip, Eric; Kelly, Virginia; Brümmendorf, Tim.
In: BLOOD, Vol. 119, No. 15, 15, 2012, p. 3403-3412.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure.
AU - Khoury, H Jean
AU - Cortes, Jorge E
AU - Kantarjian, Hagop M
AU - Gambacorti-Passerini, Carlo
AU - Baccarani, Michele
AU - Kim, Dong-Wook
AU - Zaritskey, Andrey
AU - Countouriotis, Athena
AU - Besson, Nadine
AU - Leip, Eric
AU - Kelly, Virginia
AU - Brümmendorf, Tim
PY - 2012
Y1 - 2012
N2 - Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier-estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.
AB - Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier-estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Young Adult
KW - Algorithms
KW - Chemotherapy, Adjuvant
KW - Treatment Failure
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Piperazines/administration & dosage
KW - Pyrimidines/administration & dosage
KW - Drug Resistance, Neoplasm/drug effects
KW - Aniline Compounds/pharmacology/therapeutic use
KW - Antineoplastic Agents/pharmacology/therapeutic use
KW - Leukemia, Myeloid, Chronic-Phase/drug therapy/pathology
KW - Nitriles/pharmacology/therapeutic use
KW - Quinolines/pharmacology/therapeutic use
KW - Thiazoles/administration & dosage
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Young Adult
KW - Algorithms
KW - Chemotherapy, Adjuvant
KW - Treatment Failure
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Piperazines/administration & dosage
KW - Pyrimidines/administration & dosage
KW - Drug Resistance, Neoplasm/drug effects
KW - Aniline Compounds/pharmacology/therapeutic use
KW - Antineoplastic Agents/pharmacology/therapeutic use
KW - Leukemia, Myeloid, Chronic-Phase/drug therapy/pathology
KW - Nitriles/pharmacology/therapeutic use
KW - Quinolines/pharmacology/therapeutic use
KW - Thiazoles/administration & dosage
M3 - SCORING: Journal article
VL - 119
SP - 3403
EP - 3412
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 15
M1 - 15
ER -
