FDA Approved Drugs » 2012
Medical Areas: Hematology | Oncology
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved September 2012
Treatment Area: Ph+ chronic myelogenous leukemia
Bosulif (bosutinib) is a tyrosine kinase inhibitor. Tyrosine kinases a subclass of protein kinase. Tyrosine kinases function as an on or off switch in many cellular functions. They can become mutated and cause unregulated growth of the cell, which is a necessary step for the development of cancer. Bosutinib inhibits the Bcr-Abl kinase that promotes CML amd also inhibits the Src-family kinases.
Bosulif is specifically indicated for the treatment of adults with chronic, accelerated, or blast phase Philadelphia chromosome-positive
(Ph+) chronic myelogenous leukemia with resistance or intolerance to prior therapy.
Bosulif is supplied as a tablet for oral administration. The recommended dose is 500 mg orally once daily with food. Continue treatment until disease progression or patient intolerance.
FDA ApprovalThe FDA approval of Bosulif was based on a phase I/II single arm, open-label, multicenter trial in in patients with imatinib-resistant or -intolerant CML. Subjects were enrolled in separate cohorts for chronic, accelerated, and blast phase disease previously treated with one prior TKI (imatinib) or more than one TKI (imatinib followed by dasatinib and/or nilotinib). The protocol was amended to exclude subjects with a known history of the T315I mutation after 396 subjects were enrolled in the trial. A total of 546 subjects were treated with Bosulif 500 mg once daily. Of the 546 treated subjects, 503 were considered evaluable for efficacy. Median duration of Bosulif treatment was 22 months in patients with CP CML previously treated with one TKI (imatinib), 8 months in patients with CP CML previously treated with imatinib and at least 1 additional TKI, 10 months in patients with AP CML previously treated with at least imatinib, and 3 months in patients with BP CML previously treated with at least imatinib. The efficacy endpoints for patients with CP CML previously treated with one prior TKI (imatinib) were the rate of attaining MCyR at week 24 and the duration of MCyR. The efficacy endpoints for patients with CP CML previously treated with both imatinib and at least 1 additional TKI were the cumulative rate of attaining MCyR by week 24 and the duration of MCyR. The efficacy endpoints for patients with previously treated AP and BP CML were confirmed complete hematologic response (CHR) and overall hematologic response (OHR). The results are as follows:Efficacy Results in Patients with Ph+ CP CML with Resistance to or Intolerance to Imatinib:Prior Treatment with Imatinib Only: Week 24 MCyR: 90%; Prior Treatment with Imatinib and Dasatinib or Nilotinib: Week 24 MCyR: 29%.Efficacy Results in Patients with Accelerated Phase and Blast Phase CML Previously Treated with at Least Imatinib:AP CML: CHR by Week 48: 21%; OHR by Week 48: 31% BP CML: CHR by Week 48: 9%; OHR by Week 48: 17%. Of the 69 evaluable subjects with AP CML, 4 had confirmed disease transformation to BP while on Bosulif treatment.
Adverse events associated with the use of Bosulif may include, but are not limited to, the following:
Bosutinib is a tyrosine kinase inhibitor. Bosutinib inhibits the Bcr-Abl kinase that promotes CML; it is also an inhibitor of Src-family kinases including Src, Lyn, and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms of Bcr-Abl expressed in murine myeloid
cell lines. Bosutinib did not inhibit the T315I and V299L mutant cells. In mice, treatment with bosutinib reduced the size of CML tumors relative to controls and inhibited growth of murine myeloid tumors expressing several imatinib-resistant forms of Bcr-Abl.
Cortes JE, Kim DW, Kantarjian HM, Brümmendorf TH, Dyagil I, Griskevicus L, Malhotra H, Powell C, Gogat K, Countouriotis AM, Gambacorti-Passerini C Bosutinib Versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Results From the BELA Trial. Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology 2012 Sep 4
Cortes JE, Kantarjian HM, Brümmendorf TH, Kim DW, Turkina AG, Shen ZX, Pasquini R, Khoury HJ, Arkin S, Volkert A, Besson N, Abbas R, Wang J, Leip E, Gambacorti-Passerini C Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood 2011 Oct 27;118(17):4567-76
Abbas R, Hug BA, Leister C, Gaaloul ME, Chalon S, Sonnichsen D A phase I ascending single-dose study of the safety, tolerability, and pharmacokinetics of bosutinib (SKI-606) in healthy adult subjects. Cancer chemotherapy and pharmacology 2012 Jan;69(1):221-7
For additional information regarding Bosulif or Ph+ chronic myelogenous leukemia, please visit the Bosulif web page.