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Long‐term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib
Author(s) -
Cortes Jorge E.,
Khoury Hanna J.,
Kantarjian Hagop M.,
Lipton Jeff H.,
Kim DongWook,
Schafhausen Philippe,
Matczak Ewa,
Leip Eric,
Noonan Kay,
Brümmendorf Tim H.,
GambacortiPasserini Carlo
Publication year - 2016
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24536
Subject(s) - bosutinib , medicine , nilotinib , dasatinib , imatinib , cumulative incidence , adverse effect , nausea , myeloid leukemia , gastroenterology , oncology , cohort
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 ≤35 vs. ≥95% 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. © 2017 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.