On September 26, 2023, bosutinib (Bosulif) was approved for pediatric patients aged 1 year and older with chronic-phase Philadelphia chromosome–positive chronic myeloid leukemia (CML) that is newly diagnosed or resistant or intolerant to prior therapy.¹ New capsule dosage form strengths of 50 mg and 100 mg were also approved.

Supporting Efficacy Data

Approval was supported by findings in the multicenter BCHILD trial (ClinicalTrials.gov identifier NCT04258943), in which 21 patients (median age = 14 years, range = 5–17 years) with newly diagnosed chronic-phase Philadelphia chromosome–positive CML received bosutinib at 300 mg/m² once daily, and 28 patients (median age = 11.5 years, range = 1–17 years) with resistant or intolerant chronic-phase Philadelphia chromosome–positive CML were treated at 300 mg/m² or 400 mg/m² once daily.

Among patients with newly diagnosed disease, the median follow-up was 14.2 months (range = 1.1–26.3 months). A major cytogenetic response occurred in 76.2% (95% confidence interval [CI] = 52.8%–91.8%); a complete cytogenetic response, in 71.4% (95% CI = 47.8%–88.7%); and a major molecular response, in 28.6% (95% CI = 11.3%–52.3%). Among patients with resistant or intolerant disease, the median follow-up was 23.2 months (range = 1–61.5 months). A major cytogenetic response occurred in 82.1% (95% CI = 63.1%–93.9%); a complete cytogenic response, in 78.6% (95% CI = 59%–91.7%); and a major molecular response, in 50% (95% CI = 30.6%–69.4%). Among 14 patients with a major molecular response, 2 lost the major molecular response after 13.6 and 24.7 months on treatment.

How It Is Used

The recommended doses are 300 mg/m² orally once daily for patients with newly diagnosed disease and 400 mg/m² orally once daily for those with resistant or intolerant disease, both given with food, until disease progression or unacceptable toxicity. For patients unable to swallow capsules, capsule contents can be mixed with applesauce or yogurt. Dosage modifications for such factors as myelosuppression, nonhematologic adverse reactions, and renal and hepatic impairment are provided in the product labeling.

Safety Profile

Among the 49 patients in the BCHILD study, 77.6% were exposed to treatment for at least 6 months and 51%, for at least 1 year. The most common adverse events of any grade were diarrhea (82%), abdominal pain (73%), vomiting (55%), nausea (49%), rash (49%), fatigue (37%), hepatic dysfunction (37%), headache (35%), pyrexia (31%), decreased appetite (27%), and constipation (20%). The most common grade 3 or 4 adverse events included hepatic dysfunction (14%), diarrhea (12%), and rash (8%). The most common grade 3 or 4 laboratory abnormalities were decreased platelet count (18%), increased alanine aminotransferase (ALT, 14%), and decreased neutrophil count (12%).

Adverse events led to discontinuation of treatment in 20% of patients, the most common of which were increased ALT (6%), increased aspartate aminotransferase (4%), diarrhea (4%), fatigue (4%), and maculopapular rash (4%).

Bosutinib has warnings/precautions for gastrointestinal toxicity, myelosuppression, hepatic toxicity, cardiovascular toxicity, fluid retention, renal toxicity, and embryofetal toxicity.

Bosutinib is contraindicated in patients with hypersensitivity to the agent. Concomitant use with strong and moderate CYP3A inhibitors (eg, clarithromycin, erythromycin, fluconazole) and strong CYP3A inducers (eg, glucocorticoids, rifampin, phenobarbital) should be avoided. Short-acting antacids and H2 antagonists should be used as alternatives to proton pump inhibitors. Patients should be advised not to breastfeed while receiving bosutinib. 

REFERENCE

1. Bosulif (bosutinib) tablets and capsules for oral use prescribing information, Pfizer, September 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/203341s025lbl.pdf. Accessed October 11, 2023.