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, Jorge E. Cortes, Jeff H. Lipton, Hagop M. Kantarjian, Dong Wook Kim, Philippe Schafhausen, Rocco Crescenzo, Nathalie Bardy-Bouxin, Mark Shapiro, Kay Noonan, Eric Leip, Liza Deannuntis, Tim H. Brümmendorf, H. Jean Khoury

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12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1298-1307
Number of pages10
JournalHaematologica
Volume103
Issue number8
DOIs
StatePublished - Jul 31 2018

ASJC Scopus subject areas

  • Hematology

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    Gambacorti-Passerini, C., Cortes, J. E., Lipton, J. H., Kantarjian, H. M., Kim, D. W., Schafhausen, P., Crescenzo, R., Bardy-Bouxin, N., Shapiro, M., Noonan, K., Leip, E., Deannuntis, L., Brümmendorf, T. H., & Jean Khoury, H. (2018). 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. Haematologica, 103(8), 1298-1307. https://doi.org/10.3324/haematol.2017.171249