On 26 September 2023, the US Food and Drug Administration (FDA) approved bosutinib (Bosulif, Pfizer) for paediatric patients 1 year of age and older with chronic phase (CP) Ph+ chronic myelogenous leukaemia (CML) that is newly diagnosed (ND) or resistant or intolerant (R\/I) to prior therapy. The FDA also approved a new capsule dosage form available in strengths of 50 mg and 100 mg.<\/p>\n
Full prescribing information for Bosulif is available here<\/a>.<\/p>\n Efficacy was evaluated in the BCHILD study (NCT04258943), a multicentre, non-randomised, open-label study conducted to identify a recommended bosutinib dose in paediatric patients with ND CP Ph+ CML and R\/I CP Ph+ CML, to estimate the safety and tolerability and efficacy, and to evaluate bosutinib pharmacokinetics in this patient population. The study enroled 28 patients with R\/I CP Ph+ CML treated with bosutinib at 300 mg\/m2<\/sup> to 400 mg\/m2<\/sup> orally once daily and 21 patients with ND CP Ph+ CML treated at 300 mg\/m2<\/sup> once daily.<\/p>\n The major efficacy outcome measures included major cytogenetic response (MCyR), complete cytogenetic response (CCyR), and major molecular response (MMR). For paediatric patients with ND CP Ph+ CML, the major (MCyR) and complete (CCyR) cytogenetic responses were 76.2% (95% confidence interval [CI] 52.8, 91.8) and 71.4% (95% CI 47.8, 88.7), respectively. The 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).<\/p>\n For paediatric patients with R\/I CP Ph+ CML, the major (MCyR) and complete (CCyR) cytogenetic responses were 82.1% (95% CI 63.1, 93.9) and 78.6% (95% CI 59, 91.7), respectively. The MMR was 50% (95% CI 30.6, 69.4). Among 14 patients who achieved MMR, two patients lost MMR after 13.6 and 24.7 months on treatment. The median follow-up was 23.2 months (range: 1, 61.5 months).<\/p>\n The most common adverse reactions in paediatric patients (\u226520%) were diarrhoea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite, and constipation. The most common laboratory abnormalities that worsened from baseline in paediatric patients (\u226545%) were increased creatinine, increased alanine aminotransferase or aspartate aminotransferase, decreased white blood cell count, and decreased platelet count.<\/p>\n The recommended bosutinib dose for paediatric patients with ND CP Ph+ CML is 300 mg\/m2<\/sup> orally once daily with food and the recommended dosage for paediatric patients with R\/I CP Ph+ CML is 400 mg\/m2<\/sup> 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.<\/p>\n This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment.<\/p>\n This application was granted priority review and orphan drug designation.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n