Pediatric Cancer Drug Development Lags Behind Adult Approvals, Study Finds

Most anticancer drugs that enter clinical testing in children and adolescents fail to reach late-phase trials or earn pediatric regulatory approval, according to new research published in Cancer.

Over a 15-year period, only 17.7% of anticancer drugs that entered pediatric-eligible clinical trials advanced to a pediatric phase 3 trial. The 10-year cumulative incidence of pediatric FDA approval was just 12.0% compared with 38.7% for adult FDA approval over the same window. In addition, more than one third of drugs that started pediatric clinical trials had no additional pediatric trials within a 5-year period.

The study analyzed the clinical and regulatory timelines of 191 anticancer agents, all of which initiated a first trial involving patients younger than 18 years between 2005 and 2020. Almost two thirds of the agents were small molecule inhibitors. Only 11% were FDA approved in adults at the time of their initial trial in children and adolescents.

Ten years after the initial pediatric-eligible trial, the cumulative incidence of subsequent pediatric phase 1, 2, and 3 trials was 56.1%, 63%, and 17.7%, respectively. Among drugs not already approved when their initial pediatric-eligible trial started, the 10-year cumulative incidence of subsequent pediatric FDA and European Medicines Agency (EMA) approval was 12% and 5.6%, respectively. Adult approvals were far more common, with cumulative incidence at 10 years of 38.7% for the FDA and 31.7% for the EMA.

Drugs that entered pediatric testing in a phase 1/2 or phase 2 trial were more likely to reach subsequent approval than drugs starting in phase 1, as were drugs already FDA- or EMA-approved in adults. "These results may reflect a greater a priori expectation of clinical benefit in the trial and argue for more initial dose confirmation studies in pediatric oncology," the authors wrote.

Developing pediatric anticancer drugs presents distinct challenges compared with drugs for adults. Childhood cancers are rare and biologically heterogeneous. Pediatric trials also present complex ethical concerns that may impede enrollment. Combined with poor commercial prospects, these factors yield low investment from pharmaceutical companies, resulting in relatively slower development than adult agents.

A 2019 study found that the median lag between first-in-human and first-in-child trials for oncology drugs that eventually won FDA approval was 6.5 years, with a range up to 27.7 years. A more recent analysis revealed that only 1.4% of new anticancer drugs entering clinical testing in any age group reached pediatric FDA approval within 10 years.

However, the pace of new drug approvals by the FDA for children and adolescents has significantly accelerated over the last decade. "Through incentives and hard work, we have seen exponential growth recently in FDA approvals for [pediatric] drugs," a St. Jude Children's Research Hospital official said at a recent AACR Annual Meeting. "When you look at the past 3 years, we are consistently having drugs approved for children with cancer."

Two main constraints are still holding back the pediatric pipeline: poor funding specifically for pediatric drugs and a small market size, which can result in business decisions to discontinue development.