FDA approves Bosulif (bosutinib) for pediatric Ph+ CP-CML

A new capsule dosage form available at 50 mg and 100 mg was also approved.

The regulatory decision was supported by data from the phase 1/II BCHILD trial (NCT04258943), which demonstrated that at a median follow-up of 14.2 months (range, 1.1-26.3), pediatric patients with newly diagnosed Ph-positive CP-CML (n = 21) experienced a major cytogenetic response (MCyR) rate of 76.2% (95% CI, 52.8%-91.8%) and a complete cytogenetic response (CCyR) rate of 71.4% (95% CI, 47.8%-88.7%). Additionally, the major molecular response (MMR) was 28.6% (95% CI, 11.3%-52.3%). At a median follow-up of 23.2 months (range, 1-61.5) for pediatric patients with resistant/intolerant Ph-positive CP-CML (n = 28), the MCyR and CCyR rates 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%). In the 14 patients who achieved MMR, 2 patients lost MMR after 13.6 and 24.7 months on treatment, respectively.

The multicenter, nonrandomized, open-label BCHILD trial enrolled pediatric patients between 1 and 17 years of age with a cytogenetic and molecular diagnosis of Ph-positive CML, either at the time of initial CML diagnosis or at screening. Newly diagnosed patients needed to have Ph-positive CP-CML within 6 months of initial diagnosis without any previous TKI treatment for CML, except for hydroxyurea and/or anagrelide. Patients with resistant/intolerant CP-CML needed the have resistance as defined by 2013 European Leukemia Net guidelines or intolerance to at least one prior TKI.

All patients were required to have a Lansky performance status of at least 50% (for patients less than 16 years of age) or a Karnofsky performance status of at least 50% (for patients greater than 16 years of age). Adequate bone marrow function, neutrophil count, and renal function were also required. Patients were excluded if they had primary Ph-positive acute lymphoblastic leukemia, extramedullary disease only, or documented BCR-ABL1 T315I or V299L mutations.

In phase 1, patients with resistant/intolerant Ph-positive CP-CML were treated with 400 mg/m2 of oral bosutinib once per day. Once the recommended phase II dose was established, subsequent patients with resistant/intolerant disease were treated at the RP2D in phase II. Patients with newly diagnosed were only enrolled during phase II, where they were treated with 300 mg/m2 of oral bosutinib once per day. Per the FDA, the recommended bosutinib dose for pediatric patients with newly diagnosed Ph-positive CP-CML is 300 mg/m2 orally once daily with food. The recommended dosage for pediatric patients with resistant/intolerant Ph-positive CP-CML is 400 mg/m2 orally once daily with food.

Regarding safety, the most common adverse effects reported in at least 20% of pediatric patients consisted of 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 at least 45% of pediatric patients included increased creatinine, increased alanine aminotransferase, increased aspartate aminotransferase, decreased white blood cell count, and decreased platelet count.