Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib

• Type of Material: Article
• Authors: Jorge E. Cortes, University of Texas MD Anderson Cancer Center; Hanna Khoury, Emory University; Hagop M. Kantarjian, University of Texas MD Anderson Cancer Center; Jeff H. Lipton, Princess Margaret Hospital; Dong-Wook Kim, Seoul St Marys Hospital; Philippe Schafhausen, University Cancer Center Hamburg; Ewa Matczak, Pfizer Inc; Eric Leip, Pfizer Inc; Kay Noonan, Pfizer Inc; Tim H. Bruemmendorf, University Cancer Center Hamburg; Carlo Gambacorti-Passerini, University of Milano‐Bicocca
• Language: English
• Date: 2016-12-01
• Publisher: Wiley-Blackwell
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Wiley Periodicals, Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/ajh.24536
• Title of Journal or Parent Work: American Journal of Hematology
• Volume: 91
• Issue: 12
• Start Page: 1206
• End Page: 1214
• Grant/Funding Information: This study was sponsored by Pfizer Inc. Editorial and medical writing support was provided by Johna Van Stelten, PhD, and Simon J. Slater, PhD, of Complete Healthcare Communications, LLC, and was funded by Pfizer Inc.
• Keywords: Hematology; TYROSINE KINASE INHIBITORS; Life Sciences & Biomedicine; SAFETY; Science & Technology; MOLECULAR RESPONSES; INTOLERANCE; TRIAL; FOLLOW-UP; EFFICACY; RESISTANCE; THERAPY; IN-VITRO
• Research Categories: Health Sciences, Oncology

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 ≤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. © 2016 Wiley Periodicals, Inc.