TY - JOUR
T1 - Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period
T2 - Final results of a phase I/II study
AU - Gambacorti-Passerini, Carlo
AU - Cortes, Jorge E.
AU - Lipton, Jeff H.
AU - Kantarjian, Hagop M.
AU - Kim, Dong Wook
AU - Schafhausen, Philippe
AU - Crescenzo, Rocco
AU - Bardy-Bouxin, Nathalie
AU - Shapiro, Mark
AU - Noonan, Kay
AU - Leip, Eric
AU - Deannuntis, Liza
AU - Brümmendorf, Tim H.
AU - Jean Khoury, H.
N1 - Funding Information:
The authors would like to acknowledge Dr. H. Jean Khoury for his extraordinary contributions to the research and treatment of hematologic malignancies. This study was sponsored by Pfizer Inc. Medical writing support was provided by Johna Van Stelten, PhD, of Complete Healthcare Communications, LLC, and was funded by Pfizer Inc. Dr. Jorge Cortes’ participation in this study was supported in part by NCI grants CA016672 and CA049639.
Publisher Copyright:
© 2018 Ferrata Storti Foundation.
PY - 2018/7/31
Y1 - 2018/7/31
N2 - 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.
AB - 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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U2 - 10.3324/haematol.2017.171249
DO - 10.3324/haematol.2017.171249
M3 - Article
C2 - 29773593
AN - SCOPUS:85051142821
SN - 0390-6078
VL - 103
SP - 1298
EP - 1307
JO - Haematologica
JF - Haematologica
IS - 8
ER -