儿童抗癌药物的全球格局与研发管线：一项附仪表盘生成的全面分析

Although childhood cancer survival outcomes have markedly improved over the past several decades due to therapeutic advancements, significant gaps remain in accessibility to cancer medicines for children. We aimed to analyse the global paediatric oncology landscape and pipeline of all childhood cancer medicines that are in common use or development.

We searched the International Clinical Trials Registry Platform (ICTRP) for paediatric oncology trials registered between Jan 1, 2007 and Aug 2, 2022, to identify childhood cancer medicines. From each trial's full entry and further online search across various sources, we obtained information on mechanism of action, molecular target, most recent development phase, malignancy inclusion in trials, administration route, paediatric-friendly oral formulation availability, storage requirements, and regulatory approval status for each cancer medicine. Cellular therapies were analysed separately by target, most recent development phase, malignancy inclusion in trials, and regulatory approval status. We summarise attributes of childhood cancer medicines and paediatric oncology trial conduct.

Of 5068 clinical trials downloaded from the ICTRP, 2160 met inclusion criteria for full review and data extraction. The highest clinical trial participation was in high-income countries, the majority being in the Americas (1006 trials), the Western Pacific (843 trials), and Europe (588 trials). We identified 440 unique childhood cancer medicines, excluding cellular therapy; of these, 243 (55%) medicines were either molecular targeted therapies or immunotherapies. Of 212 medicines with available information, 79 (37%) required cold storage, and 112 (55%) of 204 required light protection. Paediatric-friendly formulations were available for 57 (45%) of 126 orally administered medicines. Of the 440 cancer medicines used in paediatric cancer trials, 37 (8%) and 85 (19%) are approved for children by the European Medicines Agency (EMA) and US Food and Drug Administration (FDA), respectively, with a median approval lag time between adult and paediatric approvals of 2 years (IQR 0-7) for the EMA and 3 years (0-10) for the FDA. 274 (62%) of 440 cancer medicines were in phase 1 or 2 of development. Most cellular therapies in clinical trials were chimeric antigen receptor (CAR) T-cell therapies, targeting 48 unique antigens. INTERPRETATION: This overview of the global paediatric oncology landscape and pipeline of childhood cancer medicines highlights important barriers to improving effective treatment access for all children. Further analyses of these data, which are now publicly available on an online dashboard hosted by the WHO Global Observatory on Health Research and Development, should guide stakeholders in further investigation of clinical trial results to inform drug prioritisation for clinical development, paediatric-friendly formulations, expedited regulatory approvals, essential medicine designation, and local capacity building. FUNDING: St Jude Children's Research Hospital.