Review of Racial and Ethnic Representation of Participants Enrolled in Pediatric Clinical Trials of Oncology Drugs Conducted Through FDA Written Requests.

Importance: The Best Pharmaceuticals for Children Act states that in issuing a written request (WR), the US Food and Drug Administration (FDA) shall consider the adequate representation (eg, proportionate to the disease population) of children from racial and ethnic minority populations. If the terms of the WR are fulfilled, the FDA may grant an additional 6 months of exclusivity for any unexpired patents and exclusivities attached to approved indications. Objective: To report on the race and ethnicity of participants enrolled in pediatric studies conducted in response to WRs for which pediatric exclusivity was granted between 2001 and 2021. Design, Setting, and Participants: This retrospective review examines pediatric exclusivity request submissions for oncologic drugs that received pediatric exclusivity between December 2001 and January 2021 based on fulfillment of the requirements of a WR that were identified using the FDA's Document Archiving Reporting and Regulatory Tracking System. Demographic data were manually abstracted from supporting study reports, and data were pooled across submissions for the analysis. Data were analyzed throughout 2022 and 2023. Main Outcomes and Measures: Representation by race, sex, and ethnicity in pediatric studies conducted in response to WRs. Results: A total of 22 pediatric exclusivity requests were identified, comprising 40 studies and 2025 patients. Most trials (26 [65%]) in the analysis were cooperative group studies. Representation by race was as follows: American Indian/Alaska Native (13 [0.6%]), African American/Black (228 [11.3%]), Asian (92 [4.6%]), Native Hawaiian/other Pacific Islander (33 [1.6%]), White (1303 [64.3%]), other (194 [9.6%]), and unknown/not reported (162 [8.0%]). Representation by sex was female individuals (41.2%) and male individuals (58.8%). Ethnicity was as follows: Hispanic (226 [5.7%]), non-Hispanic (910 [22.5%]), unknown/not reported ethnicity (2800 [69.1%]), and other ethnicity (114 [2.8%]). Conclusions and Relevance: The study results suggest that overall, representation of participants of racial and ethnic minority groups in studies supporting pediatric exclusivity requests appear comparable with the racial distribution of childhood cancers in the US based on data from the National Childhood Cancer Registry Explorer. However, fewer Hispanic participants were enrolled in the trials we reviewed (8%) compared with the representation of Hispanic patients in the National Childhood Cancer Registry (28%). This discrepancy may be partially explained by the large proportion of participants with unknown information regarding ethnicity. Further research into the reasons for the large proportion of participants with missing ethnicity information is needed.

Fusion Oncoproteins in Childhood Cancers: Potential Role in Targeted Therapy.

Cancer remains the leading cause of death from disease in children. Historically, in contrast to their adult counterparts, the causes of pediatric malignancies have remained largely unknown, with most pediatric cancers displaying low mutational burdens. Research related to molecular genetics in pediatric cancers is advancing our understanding of potential drivers of tumorigenesis and opening new opportunities for targeted therapies. One such area is fusion oncoproteins, which are a product of chromosomal rearrangements resulting in the fusion of different genes. They have been identified as oncogenic drivers in several sarcomas and leukemias. Continued advancement in the understanding of the biology of fusion oncoproteins will contribute to the discovery and development of new therapies for childhood cancers. Here we review the current scientific knowledge on fusion oncoproteins, focusing on pediatric sarcomas and hematologic cancers, and highlight the challenges and current efforts in developing drugs to target fusion oncoproteins.

A review of the experience with pediatric written requests issued for oncology drug products.

BACKGROUND: Pediatric anticancer drug development has numerous challenges. The Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) were passed to address pediatric drug development deficiencies in general. Until recently, the requirements for pediatric evaluation of most oncology products developed for adult cancers have been waived. Because children typically do not have the same type of cancers, which occur commonly in adults, or the indication or drug had been granted an orphan designation, PREA therefore has had no impact. Pediatric studies for labeling updates are largely done through BPCA by a written request (WR) issued by the Food and Drug Administration (FDA). Because the cancers that occur in pediatric and adult populations do not share the same etiology or natural history, there are limited opportunities to extrapolate adult efficacy and safety to the pediatric population. The characteristics of individual pediatric studies included in WRs have varied greatly over time. PROCEDURE: In this study, we searched WRs that were issued by the FDA since 2001. We found 40 such requests issued for oncology drugs and biologics, which had been accepted by sponsors. RESULTS: Clinical trials included in 23 of the WRs have been concluded, 19 have resulted in exclusivity, and three drugs that were studied have been approved for use in pediatric populations. Herein, we present the spectrum of WRs from a regulatory, study design, dosing, formulation, analysis plan, evidentiary standard of efficacy, and safety perspective. CONCLUSIONS: This provides information on requests issued in the past nearly 20 years and studies that are completed. As WRs have provided the only regulatory mechanism to assure pediatric cancer drug development, this can potentially provide insight on how pediatric cancer drug development may change in the future.