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We evaluated vascular\/cardiac toxicities associated with long\u2010term bosutinib treatment for Philadelphia chromosome\u2010positive (Ph+) leukemia based on treatment\u2010emergent adverse events (TEAEs) and changes in QTc intervals and ejection fraction in two studies: a phase 1\/2 study of second\u2010\/third\u2010\/fourth\u2010line bosutinib for Ph+ leukemia resistant\/intolerant to prior TKIs (<jats:italic>N<\/jats:italic>\u2009=\u2009570) and a phase 3 study of first\u2010line bosutinib (<jats:italic>n<\/jats:italic>\u2009=\u2009248) versus imatinib (<jats:italic>n<\/jats:italic>\u2009=\u2009251) in chronic phase chronic myeloid leukemia. Follow\u2010up time was \u226548 months (both studies). Incidences of vascular\/cardiac TEAEs in bosutinib\u2010treated patients were 7%\/10% overall with similar incidences observed with first\u2010line bosutinib (5%\/8%) and imatinib (4%\/6%). Few patients had grade \u22653 vascular\/cardiac events (4%\/4%) and no individual TEAE occurred in &gt;2% of bosutinib patients. Exposure\u2010adjusted vascular\/cardiac TEAE rates (patients with events\/patient\u2010year) were low for second\u2010line or later bosutinib (0.037\/0.050) and not significantly different between first\u2010line bosutinib (0.015\/0.024) and imatinib (0.011\/0.017; <jats:italic>P<\/jats:italic>\u2009\u2265\u20090.267). Vascular\/cardiac events were managed mainly with concomitant medications (39%\/44%), bosutinib treatment interruptions (18%\/21%), or dose reductions (4%\/8%); discontinuations due to these events were rare (0.7%\/1.0%). Based on logistic regression modelling, performance status &gt;0 and history of vascular or cardiac disorders were prognostic of vascular\/cardiac events in relapsed\/refractory patients; hyperlipidemia\/hypercholesterolemia and older age were prognostic of cardiac events. In newly diagnosed patients, older age was prognostic of vascular\/cardiac events; history of diabetes was prognostic of vascular events. Incidences of vascular and cardiac events were low with bosutinib in the first\u2010line and relapsed\/refractory settings following long\u2010term treatment in patients with Ph+ leukemia. Am. J. Hematol. 91:606\u2013616, 2016. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.24360","type":"journal-article","created":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T04:56:23Z","timestamp":1457931383000},"page":"606-616","source":"Crossref","is-referenced-by-count":81,"title":["Long\u2010term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome\u2010positive leukemias treated with bosutinib"],"prefix":"10.1002","volume":"91","author":[{"given":"Jorge E.","family":"Cortes","sequence":"first","affiliation":[{"name":"University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Jean Khoury","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute of Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagop","family":"Kantarjian","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim H.","family":"Br\u00fcmmendorf","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum RWTH Aachen Aachen Germany"},{"name":"Universit\u00e4tsklinikum Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Mauro","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Matczak","sequence":"additional","affiliation":[{"name":"Pfizer Inc New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri","family":"Pavlov","sequence":"additional","affiliation":[{"name":"Pfizer Inc New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean M.","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Pfizer Inc Groton Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kolette D.","family":"Fly","sequence":"additional","affiliation":[{"name":"Pfizer Inc Groton Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetoslav","family":"Dimitrov","sequence":"additional","affiliation":[{"name":"Pfizer Inc New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Leip","sequence":"additional","affiliation":[{"name":"Pfizer Inc Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Pfizer Inc Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff H.","family":"Lipton","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Center Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Bernard","family":"Durand","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Gambacorti\u2010Passerini","sequence":"additional","affiliation":[{"name":"University of Milano\u2010Bicocca Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,13]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"National Comprehensive Cancer Network. 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