On September 26, the U.S. Food and Drug Administration (FDA) approved bosutinib (Bosulif) for pediatric patients aged 1 year and older with chronic-phase, Philadelphia chromosome–positive chronic myelogenous leukemia (CML) that is newly diagnosed or resistant or intolerant to prior therapy. The FDA also approved a new capsule dosage form, available in 50-mg and 100-mg doses.
BCHILD
Efficacy was evaluated in the BCHILD trial (ClinicalTrials.gov identifier NCT04258943), a multicenter, nonrandomized, open-label trial conducted to identify a recommended bosutinib dose in pediatric patients with newly diagnosed or resistant/intolerant chronic-phase, Philadelphia chromosome–positive CML; to estimate the therapy’s safety, tolerability, and efficacy; and to evaluate bosutinib pharmacokinetics in this patient population. The trial enrolled 28 patients with resistant or intolerant chronic-phase, Philadelphia chromosome–positive CML treated with bosutinib at 300 mg/m2 to 400 mg/m2 orally once daily, and 21 patients with newly diagnosed chronic-phase, Philadelphia chromosome–positive CML treated at 300 mg/m2 once daily.
The major efficacy outcome measures included major cytogenetic response, complete cytogenetic response, and major molecular response. For pediatric patients with newly diagnosed chronic-phase, Philadelphia chromosome–positive CML, the major and complete cytogenetic response rates were 76.2% (95% confidence interval [CI] = 52.8%–91.8%) and 71.4% (95% CI = 47.8%–88.7%), respectively. The major molecular response rate was 28.6% (95% CI = 11.3%–52.3%) and the median duration of follow-up was 14.2 months (range = 1.1–26.3 months).
For pediatric patients with resistant or intolerant chronic-phase, Philadelphia chromosome–positive CML, the major and complete cytogenetic response rates were 82.1% (95% CI = 63.1%–93.9%) and 78.6% (95% CI = 59%–91.7%), respectively. The major molecular response rate was 50% (95% CI = 30.6%–69.4%). Among 14 patients who achieved major molecular response, two patients lost response after 13.6 and 24.7 months on treatment, respectively. The median follow-up was 23.2 months (range = 1–61.5 months).
The most common adverse reactions in pediatric patients (≥ 20%) were diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite, and constipation. The most common laboratory abnormalities that worsened from baseline in pediatric patients (≥ 45%) were increased creatinine, increased alanine aminotransferase or aspartate aminotransferase, decreased white blood cell count, and decreased platelet count.
The recommended bosutinib dose for pediatric patients with newly diagnosed chronic-phase, Philadelphia chromosome–positive CML is 300 mg/m2 orally once daily with food; the recommended dosage for pediatric patients with resistant or intolerant chronic-phase, Philadelphia chromosome–positive CML is 400 mg/m2 orally once daily with food. For patients who are unable to swallow capsules, the contents of the capsules can be mixed with applesauce or yogurt.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review and Orphan Drug designation.
