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

Research output: Contribution to journalArticle

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
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Safety
Cytogenetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Disease Progression
src-Family Kinases
Thrombocytopenia
Nausea
Vomiting
bosutinib
Diarrhea
Therapeutics
Survival
Incidence

ASJC Scopus subject areas

  • Hematology

Cite this

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

In: Haematologica, Vol. 103, No. 8, 31.07.2018, p. 1298-1307.

Research output: Contribution to journalArticle

Gambacorti-Passerini, C, Cortes, JE, Lipton, JH, Kantarjian, HM, Kim, DW, Schafhausen, P, Crescenzo, R, Bardy-Bouxin, N, Shapiro, M, Noonan, K, Leip, E, Deannuntis, L, Brümmendorf, TH & 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, vol. 103, no. 8, pp. 1298-1307. https://doi.org/10.3324/haematol.2017.171249
Gambacorti-Passerini, Carlo ; Cortes, Jorge E. ; Lipton, Jeff H. ; Kantarjian, Hagop M. ; Kim, Dong Wook ; Schafhausen, Philippe ; Crescenzo, Rocco ; Bardy-Bouxin, Nathalie ; Shapiro, Mark ; Noonan, Kay ; Leip, Eric ; Deannuntis, Liza ; Brümmendorf, Tim H. ; Jean Khoury, H. / 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. In: Haematologica. 2018 ; Vol. 103, No. 8. pp. 1298-1307.
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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.",
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AU - Kim, Dong Wook

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AU - Crescenzo, Rocco

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