Bosutinib, a tyrosine kinase inhibitor, has been approved by the Food and Drug Administration as a treatment for chronic myeloid leukemia, based on the results of a study of 546 patients, the agency announced on Sept. 4.
The approved indication is for the treatment of adults with chronic, accelerated, or blast-phase Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) who are resistant to or cannot tolerate other treatments, including imatinib, according to the FDA and a statement issued by the manufacturer, Pfizer Inc.
Dr. Richard Pazdur
Pfizer will be marketing bosutinib as Bosulif. The new agent inhibits the Abl and Src signaling pathways, and is taken once a day at a dose of 500 mg by mouth, according to the company.
The FDA has approved other tyrosine kinase inhibitors to treat CML, including imatinib (Gleevec) in 2001, dasatinib (Sprycel) in 2006, and nilotinib (Tasigna) in 2007. With these approvals, "we are seeing improvements in the treatment of CML based on a better understanding of the molecular basis of the disease," Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s statement. He noted that these improvements have been seen in people in chronic and accelerated phases of CML.
In the international, phase I/II study, all 546 adults enrolled were treated with bosutinib; they were diagnosed with chronic, accelerated or blast phase CML, and had progressed after treatment with imatinib or with imatinib followed by dasatinib and/or nilotinib, or they could not tolerate previous treatments.
Among the patients with chronic phase CML who had been treated previously with imatinib (266 patients), almost 34% achieved a major cytogenic response (MCyR) by 24 weeks of treatment with bosutinib. Almost 53% of the patients who achieved a MCyR had a response that lasted at least 18 months, and a median duration of MCyR was not reached, according to the FDA and company statements.
Of the 108 patients with chronic phase CML who had been treated with imatinib and at least one other tyrosine kinase inhibitor, almost 27% achieved a MCyR by 24 weeks of treatment with bosutinib. About 51% of those who achieved a MCyR had a response that lasted at least 9 months, and in this group of patients, the median duration of MCyR also was not reached, according to the FDA and company statements.
The FDA also noted that among the patients with accelerated CML, who had been treated previously with a regimen that included at least imatinib, 33% had a complete hematologic response, and 55% achieved an overall hematologic response within the first 48 weeks of treatment.
Among those with blast phase CML, 15% achieved a complete hematologic response, and 28% achieved an overall hematologic response, according to the FDA.
Of the total 374 evaluable patients with chronic CML, 16 patients (4%) had confirmed disease transformation to advanced or blast phase while undergoing treatment with bosutinib.
Diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, fever, and fatigue were among the most common adverse events associated with bosutinib treatment, according to the FDA.
Bosutinib was approved as an orphan drug, a drug that is intended for a disease that affects fewer than 200,000 people in the United States. In 2012, about 5,430 people will be diagnosed with CML, according to the FDA. With improvements in therapy, as many as 26,000 people are living with the disease, and that number is expected to increase 10-fold by 2040, Pfizer added.