Purpose of review: To discuss considerations of new paradigms for clinical drug development in pediatric oncology that incorporate our expanding knowledge and complexity of molecular alterations associated with cancer; advances in cancer immunology and cellular therapy; the increasing number of new anticancer drugs, therapeutic approaches, and potential combinations; and recent initiatives by regulatory agencies to improve access to safe and effective therapies.
Recent findings: Cancer in children and adolescents is a rare event with significant long-term impact on individuals and society. Using multimodality therapy, stratified by patient and disease characteristics, the cure rate for childhood cancer exceeds 80%. Cancer genomics has transformed anticancer drug development. Understanding the genetic basis of pediatric cancers and the use of genomics for risk stratification has changed the focus of drug development from cytotoxic drugs to targeted therapeutic approaches. Advances in cancer immunology, immune checkpoint blockade, and cellular therapy offer novel approaches to harness T cells to treat cancer. To improve the outcome for children and adolescents with cancer and accelerate drug development, understanding drug and target interactions in preclinical models of pediatric cancer should be coupled with efficient clinical trial designs that incorporate biomarker selection, assessment of toxicity and drug exposure, and improved measures of response.
Summary: Clinical trials for children and adolescents with cancer evaluate cytotoxic drugs, molecularly target drugs, immunotherapy as well as combination therapies. The framework for oncology clinical trials will continually adapt to improve efficiency of trials and evaluate new therapeutic approaches.