Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors
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- Pashtoon M. Kasi
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
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- Gordon Fehringer
- Natera, Inc., Austin, TX
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- Hiroya Taniguchi
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
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- Naureen Starling
- The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom
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- Yoshiaki Nakamura
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
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- Daisuke Kotani
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
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- Thomas Powles
- Barts Cancer Institute, Queen Mary University of London ECMC, Barts Health, London, United Kingdom
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- Bob T. Li
- Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY
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- Lajos Pusztai
- Yale Cancer Center, Yale School of Medicine, New Haven, CT
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- Vasily N. Aushev
- Natera, Inc., Austin, TX
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- Ekaterina Kalashnikova
- Natera, Inc., Austin, TX
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- Shruti Sharma
- Natera, Inc., Austin, TX
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- Meenakshi Malhotra
- Natera, Inc., Austin, TX
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- Zachary P. Demko
- Natera, Inc., Austin, TX
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- Alexey Aleshin
- Natera, Inc., Austin, TX
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- Angel Rodriguez
- Natera, Inc., Austin, TX
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- Paul R. Billings
- Natera, Inc., Austin, TX
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- Axel Grothey
- West Cancer Center and Research Institute, Germantown, TN
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- Julien Taieb
- Georges Pompidou European Hospital, SIRIC-CARPEM, Université de Paris, Paris, France
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- David Cunningham
- The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom
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- Takayuki Yoshino
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
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- Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
抄録
<jats:sec><jats:title>PURPOSE</jats:title><jats:p> Earlier detection of cancer recurrence using circulating tumor DNA (ctDNA) to detect molecular residual disease (MRD) has the potential to dramatically affect cancer management. We review evidence supporting the use of ctDNA as a biomarker for detection of MRD and highlight the potential impact that ctDNA testing could have on the conduct of clinical trials. </jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p> We searched the literature using MEDLINE (via PubMed) for articles from January 1, 2000, focusing on studies that assessed ctDNA as a predictor of cancer recurrence. Broadly focused searches on ctDNA and cancer were also performed to provide additional background information. www.clinialtrials.gov was searched to identify trials that incorporate ctDNA testing. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> Numerous studies across different cancer types indicate that ctDNA-based MRD detection predicts recurrence with high sensitivity and specificity, and with lead times that precede standard imaging by up to 12 months. Recently, ctDNA testing has started being used to enroll MRD-positive patients at high risk of recurrence into trials, promising gains in statistical power that allow clinical utility to be demonstrated with smaller cohorts. Trials where ctDNA testing based-MRD detection is used to stratify patients into low or high-risk categories for treatment assignment are also ongoing. In addition, there is increasing evidence supporting the use of ctDNA dynamics or clearance as a surrogate end point, which could significantly reduce trial duration. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> ctDNA-based trial enrichment across many cancers seems likely to become increasingly common for cost- and time-reduction benefits. Trial efficiency could also benefit from using ctDNA as a surrogate end point, leading to accelerated approval of new therapeutics. A clear demonstration of efficacy from trials that use ctDNA-based MRD detection to assign treatment could transform clinical practice. </jats:p></jats:sec>
収録刊行物
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- JCO Precision Oncology
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JCO Precision Oncology (6), e2100181-, 2022-05
American Society of Clinical Oncology (ASCO)