Cortes, Jorge E; Khoury, Hanna J; Kantarjian, Hagop M; Lipton, Jeff H; Kim, Dong-Wook; Schafhausen, Philippe; Matczak, Ewa; Leip, Eric; Noonan, Kay; Brummendorf, Tim H; Gambacorti-Passerini, Carlo
American journal of hematology
2016Dec ; 91 ( 12 ) :1206-1214.
PMID : 27531525
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Cortes, Jorge E -
Khoury, Hanna J -
Kantarjian, Hagop M -
Lipton, Jeff H -
Kim, Dong-Wook -
Schafhausen, Philippe -
Matczak, Ewa -
Leip, Eric -
Noonan, Kay -
Brummendorf, Tim H -
Gambacorti-Passerini, Carlo -
ABSTRACT
Bosutinib is an Src/Abl tyrosine kinase inhibitor (TKI) indicated for adults with Ph+ chronic myeloid leukemia (CML) resistant/intolerant to prior TKIs. This long-term update of an ongoing phase 1/2 study evaluated the efficacy and safety of third-/fourth-line bosutinib in adults with chronic phase (CP) CML. Median durations of treatment and follow-up were 8.6 (range, 0.2-87.7) months and 32.7 (0.3-93.3) months, respectively. Cumulative confirmed complete hematologic response (cCHR) and major cytogenetic response (MCyR) rates were 74% (95% CI, 65-81%) and 40% (31-50%), respectively; Kaplan-Meier (K-M) probability of maintaining cCHR or MCyR at 4 years was 63% (95% CI, 50-73%) and 69% (52-81%). Cumulative incidence of on-treatment disease progression (PD)/death at 4 years was 24% (95% CI, 17-33%); K-M 4-year overall survival was 78% (68-85%). Baseline Ph+ cells ??5 vs. ??5% was prognostic of MCyR and CCyR by 3 and 6 months, increased baseline basophils was prognostic of PD/death, and no prior response to second-line TKI was prognostic of death. Common adverse events included diarrhea (83%), nausea (48%), vomiting (38%), and thrombocytopenia (39%). Bosutinib demonstrates durable efficacy and a toxicity profile similar to previous bosutinib studies in CP CML patients resistant/intolerant to multiple TKIs, representing an important treatment option for patients in this setting. This trial is registered at www.clinicaltrials.gov (NCT00261846). Am. J. Hematol. 91:1206-1214, 2016. ??2016 Wiley Periodicals, Inc. CI - ??2016 Wiley Periodicals, Inc.
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MESH
Adolescent, Adult, Aged, Aged, 80 and over, Aniline Compounds/adverse effects/*therapeutic use, Antineoplastic Agents/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Dasatinib, Disease Progression, Humans, Imatinib Mesylate, Leukemia, Myeloid, Chronic-Phase/*drug therapy/mortality, Longitudinal Studies, Middle Aged, Nitriles/adverse effects/*therapeutic use, Pyrimidines, Quinolines/adverse effects/*therapeutic use, Remission Induction, Salvage Therapy/*methods, Survival Analysis, Treatment Outcome, Young Adult
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