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Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up
Brummendorf, 2,3 Dong-Wook Kim,4 Anna G. Turkina,5 Tamas Masszi,6
Sarit Assouline,7 Simon Durrant,8 Hagop M. Kantarjian,9 H. Jean Khoury,10 Andrey Zaritskey,11 Zhi-Xiang Shen,12
Jie Jin,13 Edo Vellenga,14 Ricardo Pasquini,15 Vikram Mathews,16 Francisco Cervantes,17 Nadine Besson,18
Kathleen Turnbull,19 Eric Leip,19 Virginia Kelly,19 and Jorge E. Cortes9
Abstract
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 (n5200) or intolerant (n588) 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. 00:000–000, 2014. VC 2014 Wiley Periodicals, Inc.