AUTHOR=Ribba Benjamin , Roller Andreas , Helms Hans-Joachim , Stern Martin , Bleul Conrad TITLE=Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1058220 DOI=10.3389/fphar.2022.1058220 ISSN=1663-9812 ABSTRACT=

To support further development of model-informed drug development approaches leveraging circulating tumor DNA (ctDNA), we performed an exploratory analysis of the relationships between treatment-induced changes to ctDNA levels, clinical response and tumor size dynamics in patients with cancer treated with checkpoint inhibitors and targeted therapies. This analysis highlights opportunities for pharmacometrics approaches such as for optimizing sampling design strategies. It also highlights challenges related to the nature of the data and associated variability overall emphasizing the importance of mechanistic modeling studies of the underlying biology of ctDNA processes such as shedding, release and clearance and their relationships with tumor size dynamic and treatment effects.