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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.