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Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches.

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.

SUBMITTER: Ribba B

PROVIDER: S-EPMC10030934 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches.

Ribba Benjamin B Roller Andreas A Helms Hans-Joachim HJ Stern Martin M Bleul Conrad C

Frontiers in pharmacology 20230308

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 challen ...[more]

PMID: 36968790

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