FDA Approves Bosutinib (Bosulif) for Chronic Myeloid Leukemia (CML)

The US Food and Drug Administration (FDA) has approved the tyrosine kinase inhibitor bosutinib (Bosulif) to treat Philadelphia chromosome–positive chronic myelogenous leukemia (CML). The drug is intended for patients with chronic, accelerated, or blast phase CML who cannot tolerate or are resistant to other therapies (including imatinib).

“With the approval of tyrosine kinase inhibitors, we are seeing improvements in the treatment of CML based on a better understanding of the molecular basis of the disease,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a press release. “These improvements have been observed in chronic and accelerated phases of CML.”

In the past decade, the FDA has approved imatinib, dasatinib, and nilotinib to treat various forms of CML. These treatments have led to dramatically improved survival rates.

The trial that led to the approval of bosutinib was a single-arm clinical study that enrolled 546 adult patients with chronic, accelerated, or blast phase CML. All participants were treated with bosutinib. Patients included in the trial had either disease that had progressed after treatment-with imatinib, dasatinib, or nilotinib-or were unable to tolerate the side effects of these therapies.

Results showed 34% of patients with chronic phase CML who had been previously treated with imatinib achieved a major cytogenetic response (MCyR) after 24 weeks; in all, 52.8% of patients who achieved MCyR at some point had their response last at least 18 months. In patients previously treated with imatinib followed by dasatinib and/or nilotinib, about 27% achieved MCyR within the first 24 weeks of treatment; of those, 51.4% had their MCyR last at least 9 months.

In patients with accelerated CML previously treated with at least imatinib, 33% had complete hematologic response and 55% achieved overall hematologic response within the first 48 weeks of treatment. Meanwhile, 15% and 28% of patients with blast phase CML achieved complete hematologic response and overall hematologic response, respectively.

Adverse events associated with receiving bosutinib were anemia, fatigue, thrombocytopenia, vomiting, fever abdominal pain, rash, diarrhea, and nausea.

CML is diagnosed by detecting the Philadelphia chromosome, a chromosomal abnormality believed to be present in all cases of CML. This abnormality causes the bone marrow to make the enzyme tyrosine kinase, which causes elevated abnormal and unhealthy granulocytes. In 2012 it is estimated that CML will be diagnosed in 5,430 men and women.

An ongoing trial of 502 patients, the BELA trial, is evaluating bosutinib compared to imatinib in newly diagnosed chronic phase CML patients. Updated findings at 30 months follow-up were reported at this year's annual meeting of the American Society of Clinical Oncology. The authors concluded that bosutinib was effective for newly diagnosed chronic phase CML, and that the drug had a different toxicity profile than imatinib.