TY - JOUR
T1 - Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance
T2 - Minimum 24-month follow-up
AU - Gambacorti-Passerini, Carlo
AU - Brümmendorf, Tim H.
AU - Kim, Dong Wook
AU - Turkina, Anna G.
AU - Masszi, Tamas
AU - Assouline, Sarit
AU - Durrant, Simon
AU - Kantarjian, Hagop M.
AU - Khoury, H. Jean
AU - Zaritskey, Andrey
AU - Shen, Zhi Xiang
AU - Jin, Jie
AU - Vellenga, Edo
AU - Pasquini, Ricardo
AU - Mathews, Vikram
AU - Cervantes, Francisco
AU - Besson, Nadine
AU - Turnbull, Kathleen
AU - Leip, Eric
AU - Kelly, Virginia
AU - Cortes, Jorge E.
PY - 2014/7
Y1 - 2014/7
N2 - Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib as second-line therapy in 288 patients with chronic phase CML resistant (n=200) or intolerant (n=88) to imatinib. The cumulative response rates to bosutinib were as follows: 85% achieved/maintained complete hematologic response, 59% achieved/maintained major cytogenetic response (including 48% with complete cytogenetic response), and 35% achieved major molecular response. Responses were durable, with 2-year estimates of retaining response >70%. Two-year probabilities of progression-free survival and overall survival were 81% and 91%, respectively. The most common toxicities were primarily gastrointestinal adverse events (diarrhea [84%], nausea [45%], vomiting [37%]), which were primarily mild to moderate, typically transient, and first occurred early during treatment. Thrombocytopenia was the most common grade 3/4 hematologic laboratory abnormality (24%). Outcomes were generally similar among imatinib-resistant and imatinib-intolerant patients and did not differ with age. The longer-term results of the present analysis confirm that bosutinib is an effective and tolerable second-line therapy for patients with imatinib-resistant or imatinib-intolerant chronic phase CML. ClinicalTrials.gov Identifier: NCT00261846. Am. J. Hematol. 89:732-742, 2014.
AB - Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib as second-line therapy in 288 patients with chronic phase CML resistant (n=200) or intolerant (n=88) to imatinib. The cumulative response rates to bosutinib were as follows: 85% achieved/maintained complete hematologic response, 59% achieved/maintained major cytogenetic response (including 48% with complete cytogenetic response), and 35% achieved major molecular response. Responses were durable, with 2-year estimates of retaining response >70%. Two-year probabilities of progression-free survival and overall survival were 81% and 91%, respectively. The most common toxicities were primarily gastrointestinal adverse events (diarrhea [84%], nausea [45%], vomiting [37%]), which were primarily mild to moderate, typically transient, and first occurred early during treatment. Thrombocytopenia was the most common grade 3/4 hematologic laboratory abnormality (24%). Outcomes were generally similar among imatinib-resistant and imatinib-intolerant patients and did not differ with age. The longer-term results of the present analysis confirm that bosutinib is an effective and tolerable second-line therapy for patients with imatinib-resistant or imatinib-intolerant chronic phase CML. ClinicalTrials.gov Identifier: NCT00261846. Am. J. Hematol. 89:732-742, 2014.
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U2 - 10.1002/ajh.23728
DO - 10.1002/ajh.23728
M3 - Article
C2 - 24711212
AN - SCOPUS:84902843429
SN - 0361-8609
VL - 89
SP - 732
EP - 742
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 7
ER -