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

• Type of Material: Article
• Authors: Carlo Gambacorti-Passerini, University of Milano-Bicocca; Jorge E. Cortes, University of Texas; Jeff H. Lipton, Princess Margaret Cancer Centre; Hagop M. Kantarjian, University of Texas; Dong-Wook Kim, Seoul St. Mary’s Hospital; Philippe Schafhausen, Hubertus Wald Tumor Center; Rocco Crescenzo, Pfizer Inc; Nathalie Bardy-Bouxin, Pfizer Inc; Mark Shapiro, Pfizer Inc; Kay Noonan, Pfizer Inc; Eric Leip, Pfizer Inc; Liza DeAnnuntis, Pfizer Inc; Tim H. Bruemmendorf, Hubertus Wald Tumor Center; H Jean Khoury, Emory University
• Language: English
• Date: 2018-07-31
• Publisher: Ferrata Storti Foundation
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Ferrata Storti Foundation.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3324/haematol.2017.171249
• Title of Journal or Parent Work: Haematologica
• ISSN: 0390-6078
• Volume: 103
• Issue: 8
• Start Page: 1298
• End Page: 1307
• Grant/Funding Information: Medical writing support was provided by Johna Van Stelten, PhD, of Complete Healthcare Communications, LLC, and was funded by Pfizer Inc.; This study was sponsored by Pfizer Inc.; Dr. Jorge Cortes’ participation in this study was supported in part by NCI grants CA016672 and CA049639.
• Keywords: RESISTANCE; IMATINIB; INTOLERANCE; Life Sciences & Biomedicine; Science & Technology; Hematology
• Research Categories: Health Sciences, Oncology

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 cytogenetic 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%, respectively, at year 2 and 71% and 69% at year 5. Cumulative incidence of ontreatment 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, gastrointestinal 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 toxicity 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.