Incorporating Circulating Tumor DNA Testing Into Clinical Trials: A Position Paper by the National Cancer Institute
Lakshmi Rajdev1, Gentry G King2, Christopher H Lieu3
1Icahn School of Medicine at Mount Sinai, New York, NY.
JCO Precision Oncology
|March 6, 2025
Summary
Circulating tumor DNA (ctDNA) shows promise in gastrointestinal (GI) cancer trials. While more data are needed for late-phase trials, ctDNA can guide early-phase studies and drug development.
Area of Science:
- Oncology
- Molecular Diagnostics
- Clinical Trial Design
Background:
- Circulating tumor DNA (ctDNA) is an emerging biomarker in gastrointestinal (GI) cancers.
- Challenges exist in defining ctDNA's utility and role as a primary endpoint in therapeutic trials.
- The National Cancer Institute (NCI) established a working group to address these challenges.
Purpose of the Study:
- To evaluate current data on ctDNA in GI cancer.
- To provide guidance on incorporating ctDNA into GI cancer clinical trials.
- To assess ctDNA's role as a surrogate for prognosis and treatment guidance.
Main Methods:
- An NCI working group convened experts from GI disease groups.
- The panel reviewed data and provided recommendations on ctDNA's use in trials.
- A manuscript was drafted, revised, and approved by the panel and the Cancer Therapy Evaluation Program.
Main Results:
- ctDNA requires further validation as a primary endpoint for late-phase, standard-of-care-changing trials.
- ctDNA is supported as a primary efficacy endpoint for Phase II studies and for noninvasive drug development evaluation.
- Incorporating ctDNA requires consideration of GI cancer subtype biology and can be used as an exploratory endpoint.
Conclusions:
- Prospective trials are necessary to validate ctDNA as a surrogate endpoint for progression-free or overall survival in GI cancers.
