Abstract
Despite survival gains for many pediatric cancers since the 1970s, cancer remains the leading cause of death by disease for children and adolescents in the United States. Survivors of pediatric cancer often experience acute and long-term toxicities resulting in diminished quality of life and reduced life expectancy. Thus, development of new therapies that offer a better balance between efficacy and safety remains an urgent unmet need. Dose-finding trials for pediatric oncology products have traditionally focused on identifying the maximum tolerated dose based on evaluation of acute, dose-limiting toxicities. However, oncology drug development has largely shifted from cytotoxic chemotherapies to targeted therapies such as kinase inhibitors, mAbs, antibody-drug conjugates, and cellular products, which often have different dose-response relationships for efficacy and safety and are sometimes administered on a chronic basis. These differences between cytotoxic chemotherapies and newer targeted therapies necessitate adoption of new, tailored approaches to identify the recommended dosage for oncology products in pediatric patients. The FDA Oncology Center of Excellence's Project Optimus is working to help develop such approaches, and an FDA guidance containing recommendations for optimizing the dosage of oncology products was finalized in 2024. Some members of the pediatric oncology community have expressed concerns about the potential impact of ongoing dosage optimization efforts on development of new treatments for pediatric cancers. Herein, we clarify the FDA's perspectives on dosage optimization in pediatric oncology and affirm our commitment to collaborating with stakeholders to expedite development of more effective, better-tolerated drugs and biologics for pediatric patients with cancer.