On September 26, 2023, the FDA approved a new indication for bosutinib (Bosulif; Pfizer), a tyrosine kinase inhibitor, for the treatment of chronic-phase, Philadelphia chromosome (Ph)–positive chronic myelogenous leukemia (CML) in pediatric patients aged ≥1 years who are newly diagnosed or who are intolerant of or whose disease is resistant to previous therapy. A new capsule dosage form was also FDA approved, in 50-mg and 100-mg strengths; bosutinib was previously available only in 100-mg, 400-mg, and 500-mg tablet forms. The FDA granted this approval priority review and an orphan drug designation.
This marks the first approved indication of bosutinib for a pediatric population.
Bosutinib was previously approved for this indication only in adults, as well as for adults with accelerated- or blast-phase Ph-positive CML that is resistant to or who are intolerant of previous therapy.
This new approval was based on the results of the phase 1/2 BCHILD clinical trial (NCT04258943), a multicenter, nonrandomized, open-label study to identify a recommended dose of bosutinib for pediatric patients with newly diagnosed chronic-phase, Ph-positive CML or with chronic-phase, Ph-positive CML who had treatment-resistant disease or who were intolerant of previous treatment; to estimate the safety, tolerability, and efficacy of bosutinib; and to evaluate bosutinib’s pharmacokinetics in this patient population.
The trial included pediatric patients with chronic-phase, Ph-positive CML that was treatment resistant or who were intolerant of treatment who received bosutinib at 300 mg/m2 to 400 mg/m2 orally once daily (n=28) and pediatric patients with newly diagnosed chronic-phase, Ph-positive CML who received 300 mg/m2 of bosutinib once daily (n=21).
Major cytogenetic response (MCyR), complete cytogenetic response (CCyR), and major molecular response (MMR) were the main efficacy measures. The MCyR and CCyR rates for the pediatric patients with newly diagnosed chronic-phase, Ph-positive CML were 76.2% (95% confidence interval [CI], 52.8-91.8) and 71.4% (95% CI, 47.8-88.7), respectively. The rate of MMR 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 the pediatric patients with chronic-phase, Ph-positive CML that was treatment resistant or who were intolerant of previous treatment, the MCyR rate was 82.1% (95% CI, 63.1-93.9), the rate of CCyR was 78.6% (95% CI, 59-91.7), and the MMR rate was 50% (95% CI, 30.6-69.4). Of the 14 patients who reached MMR, 2 lost MMR after 13.6 months and 24.7 months of receiving treatment. The median follow-up was 23.2 months (range, 1-61.5 months).
“The biology of cancer is often different in children, and we need more treatments that are designed specifically for this vulnerable patient population…. [W]e are thrilled when a drug receives FDA approval for use in our youngest patients,” said Gwen Nichols, MD, Chief Medical Officer of The Leukemia & Lymphoma Society, in a press release.
The most common (≥20%) adverse events in the pediatric patient population were diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite, and constipation. The most frequent (≥45%) laboratory abnormalities in the pediatric patients that worsened from baseline were increased creatinine, increased alanine aminotransferase or aspartate aminotransferase, decreased white blood cell count, and decreased platelet count. Because serious adverse reactions, such as anaphylaxis, have occurred, bosutinib is contraindicated in patients with a history of hypersensitivity to bosutinib.
The recommended dose of bosutinib for pediatric patients with newly diagnosed chronic-phase, Ph-positive CML is 300 mg/m2 orally once daily taken with food; for pediatric patients with chronic-phase, Ph-positive CML that is treatment resistant or who are intolerant to previous treatment, the recommended dose is 400 mg/m2 orally once daily taken with food. If a patient cannot swallow the capsules, the contents of the capsules can be mixed with applesauce or yogurt.