The FDA has approved bosutinib to treat pediatric patients with Philadelphia chromosome–positive, chronic-phase chronic myelogenous leukemia.
The FDA has approved bosutinib (Bosulif) for a pediatric indication of Philadelphia chromosome (Ph)–positive, chronic phase–chronic myelogenous leukemia (CP–CML). The intended recipients are patients with newly diagnosed disease or those who were either resistant or intolerant to prior therapies.
Of note, the FDA also approved a new capsule dosage form of the drug. The capsules come in strengths of 50 mg and 100 mg. For children who are not able to swallow capsules, the contents can be mixed with applesauce or yogurt.
Efficacy data from the BCHILD trial (NCT04258943) supported the approval. This open-label, nonrandomized, multicenter trial was powered to find the recommended dose in this patient population, as well as to define the safety and efficacy profile associated with treatment. Participants included 28 patients with resistant or intolerant Ph+ CP–CML and 21 patients with newly diagnosed Ph+ CP–CML. Newly diagnosed patients received treatment at a dose of 300 mg/m2 once daily, and patients with resistant or intolerant disease received a dose from 300 mg/m2 to 400 mg/m2.
In the newly diagnosed subgroup, the rate of major cytogenetic response (MCyR) was 76.2% (95% CI; 52.8-91.8). The rate of complete cytogenetic response (CCyR) was 71.4% (95% CI; 47.8-88.7). The major molecular response (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).
In the resistant or intolerant population, the rate of MCyR and CCyR was 82.1% (95% CI: 63.1, 93.9) and 78.6% (95% CI: 59, 91.7), respectively. The rate of MMR was 50% (95% CI: 30.6, 69.4). There were 14 patients who achieved MMR, of these patients, 2 lost MMR after 13.6 months and 24.7 months of treatment, respectively. The median follow-up was 23.2 months (range, 1-61.5).
For patients who are newly diagnosed, the recommended dose is 300 mg/m2 orally once daily with food. For patients who are either resistant or intolerant to prior therapies, the recommended dose is 400 mg/m2 orally once daily with food.
The most common adverse events reported in at least 20% of patients in the trial included diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite, and constipation. Laboratory abnormalities, that worsened from baseline in over 45% of participants, included increased creatinine, increased alanine aminotransferase or aspartate aminotransferase, decreased white blood cell count, and decreased platelet count.