Drug development trajectory of anticancer drugs after initial pediatric-eligible trials

Attrition of new therapies is a major concern in oncology drug development. Little is known about subsequent drug development milestones once an oncology agent has entered clinical testing in children and adolescents.

This study identified 191 cancer drugs that first entered clinical trials between 2005 and 2020 and for which patients <18 years were eligible. The authors tracked subsequent drug development and regulatory milestones through 2025. They calculated Kaplan-Meier cumulative incidence rates of reaching each milestone, and they calculated Cox hazard rates according to features of the drug and trial characteristics.

The majority (62.8%) of the 191 identified drugs were small molecule inhibitors. The majority of trials evaluated single agents (66.5%) and were multicenter trials (77.9%). At 10 years from first pediatric-eligible trials, the cumulative incidence rates of subsequent phase 1, phase 2, and phase 3 trials were 56.1%, 63.0%, and 17.7%, respectively. Of 191 drugs, 71 (37.2%) had no new trials that allowed patients <18 years of age for 5 or more years from first pediatric-eligible trial. For drugs not already approved at time of initial pediatric-eligible trial, the 10-year cumulative incidence rates for subsequent pediatric Food and Drug Administration and European Medicines Agency approval were 12.0% and 5.6%, respectively. Initial trial phase and drug regulatory status at time of initial pediatric-eligible trial were the most consistent determinants of achieving subsequent drug development milestones.

Oncology drugs entering testing in children and adolescents are at high risk of attrition, including low rates of subsequent late phase trials and pediatric regulatory approvals.