Success rates for US and Canadian anticancer drug development efforts in pediatric oncology

Background Approximately 5% of adult cancer interventions put into clinical testing attain regulatory approval. Little is known about corresponding rates for pediatric cancer. Methods Our primary outcomes were the proportion of interventions graduating to the next trial phase, randomized trials, and/or clinical practice. We created a saturation sample of clinical trials by searching ClinicalTrials.gov for all pediatric anticancer trials in the United States or Canada. Trial characteristics were extracted automatically from ClinicalTrials.gov records, and cancer indication/drug class categorization, biomarker enrichment, and Food and Drug Administration (FDA) approval status at time of recruitment were double-extracted from each record. Regulatory approval status and labeling modifications for each intervention were determined by searching Drugs@FDA and the New Pediatric Labeling Information Database. Results Five hundred eighty-nine pediatric trials launched between 1987 and 2019 were captured. The overall probability of graduation was 17.0%; 18.9% of interventions graduated from phase 1 to phase 2 trials, and 1.6% of interventions graduated from phase 2 to phase 3 trials. The proportion of interventions advancing from phase 1 to FDA approval was 3.6%, and 1.9% of interventions tested in phase 1 advanced to a randomized phase 2 trial. Only biomarker enrichment was significantly predictive of graduation from phase 1 to phase 2 trials (p = .011). Conclusion The proportion of interventions advancing from phase 1 testing to FDA approval was similar to estimates for adult oncology. Our findings highlight the challenges for current paradigms of pediatric anticancer drug development.