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U.S. Department of Health and Human Services

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Bosutinib tablets

On September 4, 2012, the U. S. Food and Drug Administration approved bosutinib tablets (Bosulif, Pfizer, Inc.) for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) in adult patients with resistance or intolerance to prior therapy. 

 
The approval was based on a single-arm, open-label, multi-center trial which enrolled 546 patients with either chronic phase (CP), accelerated phase (AP) or blast phase (BP) CML previously treated with at least one prior tyrosine kinase inhibitor (TKI).  All patients received prior imatinib therapy. In the total patient population, 73% were imatinib resistant and 27% were imatinib intolerant.  In this trial, 53% of patients were males, 65% were Caucasian, and 20% were 65 years old or older. The efficacy endpoints for patients with CP CML were the rate of major cytogenetic response (MCyR) at week 24 and the duration of MCyR. The efficacy endpoints for patients with AP or BP CML were the rate of confirmed complete hematologic response (CHR) and overall hematologic response (OHR) by week 48. 
 
Patients were evaluable for efficacy if they had received at least one bosutinib dose and had a valid baseline efficacy assessment. Of the 546 patients enrolled, 503 were evaluable for efficacy. Among the patients in CP evaluable for efficacy, 266 received prior treatment with only imatinib and 108 received prior treatment with imatinib followed by either dasatinib and/or nilotinib. The trial enrolled 129 evaluable patients with advanced phase CML previously treated with at least one TKI.
 
In patients with CP CML who received prior therapy with one TKI, 90 [33.8% (95% CI: 28.2, 39.9)] achieved MCyR at week 24. Among the CP CML patients who received prior therapy with more than one TKI, 29 [26.9% (95% CI: 18.8, 36.2)] achieved MCyR by week 24. In patients with AP CML who received at least one prior TKI, 21 [30.4% (95% CI: 19.9, 42.7)] achieved CHR and 38 [55.1% (95% CI: 42.6, 67.1)] achieved OHR by week 48.  For the BP population, 9 patients [15% (95% CI: 7.1, 26.6)] achieved a CHR and 17 patients [28.3% (95% CI: 17.5, 41.4)] achieved an OHR by week 48.
 
Among the patients with CP CML who had been treated with one prior TKI (imatinib), 53.4% achieved MCyR at any time during the trial. Among these patients, 52.8% had a MCyR lasting at least 18 months. For the 32.4% of patients with CP CML treated with imatinib and at least one additional TKI who achieved a MCyR at any time, 51.4% had a MCyR lasting at least 9 months. 
 
Safety data were evaluated in 546 patients with Ph+ CML. There were 287 patients with CP CML previously treated with only imatinib who had a median bosutinib treatment duration of 24 months. There were 119 patients with CP CML previously treated with imatinib and at least 1 additional TKI who had a median bosutinib treatment duration of 9 months.  There were 76 patients with AP CML, and 64 patients with BP CML.  In these patients the median treatment duration was 10 months and 3 months, respectively.
 
The most common adverse reactions (>20%) of any grade in the safety population were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue.  Serious adverse reactions reported include anaphylactic shock, myelosuppression, gastrointestinal toxicity (diarrhea), fluid retention, hepatoxicity and rash.
 
The recommended dose and schedule for bosutinib is 500 mg orally once daily with food. Treatment is to be continued until disease progression or patient intolerance.
 
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf
 
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).