FDA approves 3rd-generation TKI for CML

The FDA has approved bosutinib (Bosulif), an Abl and Src kinase inhibitor, to treat patients with relapsed or refractory chronic myelogenous leukemia (CML).

Bosutinib is intended for use in patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive CML who have failed therapy with first-generation and second-generation tyrosine kinase inhibitors (TKIs).

The recommended dose of bosutinib is 500 mg, taken once daily with food.

“[Bosutinib] is an important new addition to the CML treatment landscape,” said Jorge E. Cortes, MD, of MD Anderson Cancer Center in Houston.

“Despite recent advances, an unmet need remains for many CML patients who are refractory to one or more tyrosine kinase inhibitors.”

Dr Cortes was a lead investigator of the industry-sponsored study that led to bosutinib’s approval. The phase 1/2 trial included 546 adult patients who had chronic, accelerated, or blast phase CML.

Efficacy data

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 chronic phase, 266 received prior treatment with imatinib only, and 108 received prior treatment with imatinib followed by dasatinib and/or nilotinib. There were 129 evaluable patients with advanced phase CML who were previously treated with at least one TKI.

The efficacy endpoints for patients with chronic phase CML were the rate of major cytogenetic response (MCyR) at week 24 and the duration of MCyR. The efficacy endpoints for patients with accelerated phase or blast phase CML were the rates of complete hematologic response (CHR) and overall hematologic response (OHR) by week 48.

In patients with chronic phase CML who received prior therapy with one TKI, 90 patients (33.8%) achieved an MCyR at week 24. Among the chronic phase CML patients who received prior therapy with more than one TKI, 29 (26.9%) achieved an MCyR by week 24.

Of the patients with chronic phase CML who had been treated with one prior TKI, 53.4% achieved an MCyR at any time during the trial. And 52.8% had a response lasting at least 18 months.

For the 32.4% of patients with chronic phase CML treated with more than one TKI who achieved an MCyR at any time, 51.4% had a response lasting at least 9 months.

In patients with accelerated phase CML who received at least one prior TKI, 21 (30.4%) achieved a CHR by week 48. And 38 patients (55.1%) achieved an OHR.

In the blast phase population, 9 patients (15%) achieved a CHR by week 48. And 17 patients (28.3%) achieved an OHR.

Safety data

The researchers evaluated bosutinib’s safety in all 546 patients. Of these patients, 287 had chronic phase CML, were previously treated with a single TKI, and had a median bosutinib treatment duration of 24 months.

There were 119 patients who had chronic phase CML, were previously treated with more than one TKI, and had a median bosutinib treatment duration of 9 months.

There were also 76 patients with accelerated phase CML and 64 patients with blast phase CML.  In these patients, the median treatment duration was 10 months and 3 months, respectively.

The most common adverse events observed in more than 20% of all patients were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue.

The most common grade 3 to 4 adverse events observed in more than 10% of patients were thrombocytopenia, anemia, and neutropenia. Other serious adverse events included anaphylactic shock, myelosuppression, gastrointestinal toxicity, fluid retention, hepatoxicity, and rash.

Bosutinib is marketed as Bosulif by Pfizer. For more information on bosutinib, see the package insert.

The FDA has approved bosutinib (Bosulif), an Abl and Src kinase inhibitor, to treat patients with relapsed or refractory chronic myelogenous leukemia (CML).

Bosutinib is intended for use in patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive CML who have failed therapy with first-generation and second-generation tyrosine kinase inhibitors (TKIs).

The recommended dose of bosutinib is 500 mg, taken once daily with food.

“[Bosutinib] is an important new addition to the CML treatment landscape,” said Jorge E. Cortes, MD, of MD Anderson Cancer Center in Houston.

“Despite recent advances, an unmet need remains for many CML patients who are refractory to one or more tyrosine kinase inhibitors.”

Dr Cortes was a lead investigator of the industry-sponsored study that led to bosutinib’s approval. The phase 1/2 trial included 546 adult patients who had chronic, accelerated, or blast phase CML.

Efficacy data

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 chronic phase, 266 received prior treatment with imatinib only, and 108 received prior treatment with imatinib followed by dasatinib and/or nilotinib. There were 129 evaluable patients with advanced phase CML who were previously treated with at least one TKI.

The efficacy endpoints for patients with chronic phase CML were the rate of major cytogenetic response (MCyR) at week 24 and the duration of MCyR. The efficacy endpoints for patients with accelerated phase or blast phase CML were the rates of complete hematologic response (CHR) and overall hematologic response (OHR) by week 48.

In patients with chronic phase CML who received prior therapy with one TKI, 90 patients (33.8%) achieved an MCyR at week 24. Among the chronic phase CML patients who received prior therapy with more than one TKI, 29 (26.9%) achieved an MCyR by week 24.

Of the patients with chronic phase CML who had been treated with one prior TKI, 53.4% achieved an MCyR at any time during the trial. And 52.8% had a response lasting at least 18 months.

For the 32.4% of patients with chronic phase CML treated with more than one TKI who achieved an MCyR at any time, 51.4% had a response lasting at least 9 months.

In patients with accelerated phase CML who received at least one prior TKI, 21 (30.4%) achieved a CHR by week 48. And 38 patients (55.1%) achieved an OHR.

In the blast phase population, 9 patients (15%) achieved a CHR by week 48. And 17 patients (28.3%) achieved an OHR.

Safety data

The researchers evaluated bosutinib’s safety in all 546 patients. Of these patients, 287 had chronic phase CML, were previously treated with a single TKI, and had a median bosutinib treatment duration of 24 months.

There were 119 patients who had chronic phase CML, were previously treated with more than one TKI, and had a median bosutinib treatment duration of 9 months.

There were also 76 patients with accelerated phase CML and 64 patients with blast phase CML.  In these patients, the median treatment duration was 10 months and 3 months, respectively.

The most common adverse events observed in more than 20% of all patients were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue.

The most common grade 3 to 4 adverse events observed in more than 10% of patients were thrombocytopenia, anemia, and neutropenia. Other serious adverse events included anaphylactic shock, myelosuppression, gastrointestinal toxicity, fluid retention, hepatoxicity, and rash.

Bosutinib is marketed as Bosulif by Pfizer. For more information on bosutinib, see the package insert.

The FDA has approved bosutinib (Bosulif), an Abl and Src kinase inhibitor, to treat patients with relapsed or refractory chronic myelogenous leukemia (CML).

Bosutinib is intended for use in patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive CML who have failed therapy with first-generation and second-generation tyrosine kinase inhibitors (TKIs).

The recommended dose of bosutinib is 500 mg, taken once daily with food.

“[Bosutinib] is an important new addition to the CML treatment landscape,” said Jorge E. Cortes, MD, of MD Anderson Cancer Center in Houston.

“Despite recent advances, an unmet need remains for many CML patients who are refractory to one or more tyrosine kinase inhibitors.”

Dr Cortes was a lead investigator of the industry-sponsored study that led to bosutinib’s approval. The phase 1/2 trial included 546 adult patients who had chronic, accelerated, or blast phase CML.

Efficacy data

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 chronic phase, 266 received prior treatment with imatinib only, and 108 received prior treatment with imatinib followed by dasatinib and/or nilotinib. There were 129 evaluable patients with advanced phase CML who were previously treated with at least one TKI.

The efficacy endpoints for patients with chronic phase CML were the rate of major cytogenetic response (MCyR) at week 24 and the duration of MCyR. The efficacy endpoints for patients with accelerated phase or blast phase CML were the rates of complete hematologic response (CHR) and overall hematologic response (OHR) by week 48.

In patients with chronic phase CML who received prior therapy with one TKI, 90 patients (33.8%) achieved an MCyR at week 24. Among the chronic phase CML patients who received prior therapy with more than one TKI, 29 (26.9%) achieved an MCyR by week 24.

Of the patients with chronic phase CML who had been treated with one prior TKI, 53.4% achieved an MCyR at any time during the trial. And 52.8% had a response lasting at least 18 months.

For the 32.4% of patients with chronic phase CML treated with more than one TKI who achieved an MCyR at any time, 51.4% had a response lasting at least 9 months.

In patients with accelerated phase CML who received at least one prior TKI, 21 (30.4%) achieved a CHR by week 48. And 38 patients (55.1%) achieved an OHR.

In the blast phase population, 9 patients (15%) achieved a CHR by week 48. And 17 patients (28.3%) achieved an OHR.

Safety data

The researchers evaluated bosutinib’s safety in all 546 patients. Of these patients, 287 had chronic phase CML, were previously treated with a single TKI, and had a median bosutinib treatment duration of 24 months.

There were 119 patients who had chronic phase CML, were previously treated with more than one TKI, and had a median bosutinib treatment duration of 9 months.

There were also 76 patients with accelerated phase CML and 64 patients with blast phase CML.  In these patients, the median treatment duration was 10 months and 3 months, respectively.

The most common adverse events observed in more than 20% of all patients were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue.

The most common grade 3 to 4 adverse events observed in more than 10% of patients were thrombocytopenia, anemia, and neutropenia. Other serious adverse events included anaphylactic shock, myelosuppression, gastrointestinal toxicity, fluid retention, hepatoxicity, and rash.

Bosutinib is marketed as Bosulif by Pfizer. For more information on bosutinib, see the package insert.