Page 62 - Haematologica August 2018

Correspondence:
carlo.gambacorti@unimib.it
Received: April 21, 2017. Accepted: May 10, 2018. Pre-published: May 17, 2018.
doi:10.3324/haematol.2017.171249
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/8/1298
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Haematologica 2018 Volume 103(8):1298-1307
6 5,10 11 DeAnnuntis, Tim H. Brümmendorf, and H. Jean Khoury *
Ferrata Storti Foundation
Chronic Myeloid Leukemia
Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase
I/II study
Carlo Gambacorti-Passerini,1 Jorge E. Cortes,2 Jeff H. Lipton,3 Hagop M.
Kantarjian,2 Dong-Wook Kim,4 Philippe Schafhausen,5 Rocco Crescenzo,6
Nathalie Bardy-Bouxin,7 Mark Shapiro,8 Kay Noonan,9 Eric Leip,8 Liza
1University of Milano-Bicocca, Monza, Italy; 2University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Princess Margaret Cancer Centre, Toronto, ON, Canada; 4Seoul St. Mary’s Hospital, South Korea; 5Department of Internal Medicine II, Hubertus Wald Tumor Center - University Cancer Center Hamburg, Germany; 6Pfizer Inc., Collegeville, PA, USA; 7Pfizer Global Research and Development, Paris, France; 8Pfizer Inc., Cambridge, MA, USA; 9Pfizer Inc., Groton, CT, USA; 10Universitätsklinikum RWTH Aachen, Germany and 11Winship Cancer Institute of Emory University, Atlanta, GA, USA.
ABSTRACT
Bosutinib is a Src/Abl tyrosine kinase inhibitor indicated for adults with newly-diagnosed Philadelphia positive chronic myeloid leukemia or with resistant/intolerant disease. We report the final results of a phase I/II study of second-line bosutinib in chronic phase chronic myeloid leukemia patients after imatinib failure (n=284). Median follow up and treatment durations were 54.8 (range 0.6-96.3) and 25.6 (0.2-96.3) months, respectively. At years 2 and 5, 54% and 40% of patients, respectively, remained on bosutinib. Cumulative major cytoge- netic response and complete cytogenetic response rates (newly-attained or maintained from baseline) were 58% and 46%, respectively, by year 2 and 60% and 50% by year 5. Kaplan-Meier probability of maintaining major and complete cytogenetic response was 76% and 78%, respective- ly, at year 2 and 71% and 69% at year 5. Cumulative incidence of on- treatment disease progression/death was similar at years 5 (19%) and 2 (15%); Kaplan-Meier overall survival was 91% at year 2 and 84% at year 5. Of 169 patients who had discontinued bosutinib by year 5, 38 did so after year 2, most commonly for disease progression (n=11). Most adverse events initially occurred within two years. Overall, gastrointesti- nal events were the most common (diarrhea 86%, nausea 46%, vomiting 37%); the most common grade 3/4 toxicity was thrombocytopenia (25%). None of the 4 on-treatment deaths in years 3-5 were related to bosutinib. Bosutinib demonstrated durable efficacy and manageable tox- icity through year 5 confirming its importance in the treatment of chronic phase chronic myeloid leukemia patients resistant/intolerant to prior imatinib. This trial was registered at clinicaltrials.gov identifier: 00261846.
Introduction
With the success of BCR-ABL1 tyrosine kinase inhibitors (TKIs), patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) can potentially enjoy a normal life expectancy.1,2 Therefore, information regarding long- term efficacy and tolerability of TKIs is important for informing treatment selec- tion.
*Deceased
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