FDA approves Bosulif for children with chronic myelogenous leukemia
The FDA expanded the approval of bosutinib to include treatment of certain children with chronic myelogenous leukemia.
The indication applies to use of the agent by pediatric patients aged 1 year or older with chronic phase Philadelphia chromosome-positive (Ph+) CML that is newly diagnosed or resistant or intolerant to prior therapy.
Bosutinib (Bosulif, Pfizer) — an oral tyrosine kinase inhibitor — previously had been approved for treatment of adults with newly diagnosed chronic phase Ph+ CML, as well as those with chronic, accelerated or blast phase Ph+ CML resistant to or intolerant of prior therapy.
The FDA based the new indication on results of the nonrandomized, multicenter BCHILD trial, designed to evaluate the efficacy and safety of bosutinib for children with newly diagnosed chronic phase Ph+ CML or relapsed/intolerant chronic phase Ph+ CML.
The trial included 28 patients with relapsed/intolerant chronic phase Ph+ CML who received bosutinib at doses ranging from 300 mg/m2 to 400 mg/m2 orally once daily, plus 21 patients with newly diagnosed chronic phase Ph+ CML who received 300 mg/m2 once daily.
Median follow-up was 14.2 months (range, 1.1-26.3) for children with newly diagnosed chronic phase Ph+ CML. Researchers reported a 76.2% (95% CI; 52.8-91.8) major cytogenetic response rate, a 71.4% (95% CI; 47.8-88.7) complete cytogenetic response rate and a 28.6% (95% CI; 11.3-52.3) major molecular response rate.
Median follow-up was 23.2 months (range, 1-61.5) for children with relapsed/intolerant chronic phase Ph+ CML. Researchers reported an 82.1% (95% CI; 63.1-93.9) major cytogenetic response rate, a 78.6% (95% CI, 59-91.7) complete cytogenetic response rate and a 50% (95% CI, 30.6-69.4) major molecular response rate.
Fourteen patients achieved major molecular response. Two lost it — one after 13.6 months on treatment and the other after 24.7 months.
The most common adverse events that occurred among at least 20% of children treated with bosutinib included diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite and constipation.
The most common laboratory abnormalities that worsened from baseline included increased creatinine, increased alanine aminotransferase or aspartate aminotransferase, decreased white blood cell count and decreased platelet count.
Perspective
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Children are in desperate need of new therapies that are effective, safe and labeled for children so that they will be covered by insurance. Off-label use of agents approved for adults may be lifesaving, but it is short-changing our kids. Going through the process of getting drugs approved in pediatric cancer is a costly proposition.
We applaud the manufacturer for completing this study. However, we need to take a critical look at why the adult approval happened in 2012 and the pediatric approval didn’t happen until more than a decade later. This means a decade in which children couldn’t reliably get access to an effective agent. It is tempting to point fingers, but this is a rare disease, and we need better alignment for international trials.
This is an operational failure in which all parties play a role, and we need to do better.
We can no longer work in silos as we try to fuel treatment developments for pediatric cancer; rather, we must get all of the pivotal stakeholders from around the world to collaborate and move the needle forward at a much quicker pace.
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