PMU56 IMPACT OF FDA APPROVAL OF NEW AGENTS ON THERAPEUTIC OPTIONS FOR GENETIC VARIANTS IN PEDIATRIC TUMORS

Providing therapy tailored to an individual patient’s genetic makeup is a fundamental hope of precision medicine. This requires both identification of genetic features and available therapeutics. Joint Consensus Recommendations for genetic variant significance (Li, et al. J Mol Diagn, 2017) include availability of any FDA approved targeting agent, inclusion in treatment guidelines, and quality of evidence regarding prognostic or therapeutic outcomes. This analysis examines the impact of new FDA approved agents on the classification of most highly significant genetic variants in pediatric malignancies over time. Whole exome sequencing was performed on 230 pediatric tumors between 2012 and 2016 as part of the BASIC3 study. Genetic variants were categorized into Joint Consensus tiers in 2019. FDA approved-agents were identified for Tier I and II variants by searching GeneCards® (genecards.org), excluding DNA/RNA and microtubular inhibitors. Year of first FDA approval was captured from FDA.com. Available agents were considered for 3 timeframes: prior to 2012, 2012-2016, and 2017-2019. In 2019, 38 Tier I/II variants were identified in one or more tumors. Before 2012, 12 FDA approved agents were available for 11 of those variants. Between 2012 and 2016, 9 new agents applying to 10 variants received FDA approval; 6 variants already had targeted agents. Between 2017 and 2019, 8 new agents applying to 7 targets received FDA approval, all variants had existing therapeutic agents. In 2019, 61% of all Tier I/II variants had no FDA approved agents. The remaining 39% had an average of 2.9 (range 1-5) potential options. Despite 17 new agents receiving FDA approval between 2012 and 2019 targeting variants in our population, only 3 (17.6%) of impacted variants without options prior to 2012. Impacts on medical decision making and patient outcomes are under further study.