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Cancer Drug Information

  • Updated: 07/01/2013

FDA Approval for Bosutinib

Brand name(s): Bosulif®

  • Approved for Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML)

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

On September 4, 2012, the Food and Drug Administration (FDA) approved bosutinib tablets (Bosulif®, made by 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 multicenter trial that enrolled 546 patients with chronic phase (CP), accelerated phase (AP), or blast phase (BP) CML previously treated with at least one tyrosine kinase inhibitor (TKI) (imatinib or imatinib followed by dasatinib and/or nilotinib). All patients received prior imatinib therapy. In the total patient population, 73 percent were imatinib resistant and 27 percent were imatinib intolerantIn this trial, 53 percent of patients were males, 65 percent were Caucasian, and 20 percent 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 evaluable patients, there were 266 with CP who had received prior treatment with only imatinib and 108 with CP who had received prior treatment with imatinib followed by either dasatinib and/or nilotinib. The remaining 129 evaluable patients had advanced phase (i.e., AP, 69 patients, or BP, 60 patients) CML previously treated with at least one TKI.

In patients with CP CML who received prior therapy with one prior TKI (imatinib), 90 [33.8 percent (95 percent CI: 28.2, 39.9)] achieved MCyR at week 24. Among the CP CML patients who received prior therapy with more than one TKI (imatinib followed by dasatinib and/or nilotinib), 29 [26.9 percent (95 percent 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 percent (95 percent CI: 19.9, 42.7)] achieved CHR and 38 [55.1 percent (95 percent CI: 42.6, 67.1)] achieved OHR by week 48. For the BP population, 9 patients [15 percent (95 percent CI: 7.1, 26.6)] achieved a CHR and 17 patients [28.3 percent (95 percent 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 percent achieved MCyR at any time during the trial. Among these patients, 52.8 percent had a MCyR lasting at least 18 months. For the 32.4 percent of patients with CP CML treated with imatinib and at least one additional TKI who achieved a MCyR at any time, 51.4 percent had a MCyR lasting at least 9 months. 

Safety data were evaluated in all 546 patients with Ph+ CML. Of these, 287 patients with CP CML previously treated with only imatinib had a median bosutinib treatment duration of 24 months. Another 119 patients with CP CML previously treated with imatinib and at least one additional TKI had a median bosutinib treatment duration of 9 months. The 76 patients with AP CML had a median bosutinib treatment duration of 10 months. The 64 patients with BP CML had a median bosutinib treatment duration of 3 months.

The most common adverse reactions (more than 20 percent) 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.

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

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