Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab
Abstract
Immune checkpoint blockade (ICB) provides clinical benefit to a subset of patients with cancer. However, existing biomarkers do not reliably predict treatment response across diverse cancer types. Limited data exist to show how serial circulating tumor DNA (ctDNA) testing may perform as a predictive biomarker in patients receiving ICB. We conducted a prospective phase II clinical trial to assess ctDNA in five distinct cohorts of patients with advanced solid tumors treated with pembrolizumab (NCT02644369). We applied bespoke ctDNA assays to 316 serial plasma samples obtained at baseline and every three cycles from 94 patients. Baseline ctDNA concentration correlated with progression-free survival, overall survival, clinical response and clinical benefit. This association became stronger when considering ctDNA kinetics during treatment. All 12 patients with ctDNA clearance during treatment were alive with median 25 months follow up. This study demonstrates the potential for broad clinical utility of ctDNA-based surveillance in patients treated with ICB.
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Recent data suggest that serial ctDNA analyses may have clinical value because ctDNA clearance in patients receiving systemic chemo- or immunotherapy correlates with progression-free and overall survival.
“recent data suggests that serial analyses may have clinical value as clearance of ctDNA among patients undergoing systemic chemo- or immunotherapy correlate with progression-free and overall survival.13–17”
From Early Changes in Circulating Cell-Free <i>KRAS</i> G12C Predict Response to Adagrasib in KRAS Mutant Non–Small Cell Lung Cancer Patients (2023) · cites this paper as [13]
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- Authors
- Bratman, S. V., Yang, S. Y. C., Iafolla, M. A. J., Liu, Z., Hansen, A. R., Bedard, P. L., Lheureux, S., Spreafico, A., Razak, A. A., Shchegrova, S., Louie, M., Billings, P., Zimmermann, B., Sethi, H., Aleshin, A., Torti, D., Marsh, K., Eagles, J., Cirlan, I., Hanna, Y., Clouthier, D. L., Lien, S. C., Ohashi, P. S., Xu, W., Siu, L. L., & Pugh, T. J.
- Affiliations
- University Health Network (CA)
- Natera (United States) (US)
- Ontario Institute for Cancer Research (CA)
- Corresponding author
- Siu, Lillian L.
- Pugh, Trevor J.
- ORCID
- Bratman, Scott V.
- Yang, S. Y. Cindy
- Iafolla, Marco A. J.
- Liu, Zhihui
- Hansen, Aaron R.
- Bedard, Philippe L.
- Spreafico, Anna
- Billings, Paul
- Zimmermann, Bernhard
- Sethi, Himanshu
- Aleshin, Alexey
- Torti, Dax
- Marsh, Kayla
- Eagles, Jenna
- Cirlan, Iulia
- Hanna, Youstina
- Lien, Scott C.
- Ohashi, Pamela S.
- Xu, Wei
- Siu, Lillian L.
- Pugh, Trevor J.
- Venue
- Nature Cancer
- Published
- 2020-08-03
- Volume
- 1
- Issue
- 9
- Pages
- 873-881
- ISSN
- 2662-1347 (ISSN-L)
- OpenAlex
- W3047097799
- Cited by
- 487
- References
- 33
- Citations by year
- 2026: 48 · 2025: 90 · 2024: 89 · 2023: 94 · 2022: 85 · 2021: 69 · 2020: 12
- FWCI
- 23.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Princess Margaret Cancer Foundation (Gattuso-Slaight Personalized Cancer Medicine Fund, BMO Chair in Precision Cancer Genomics)
- UofT | Department of Medical Biophysics, University of Toronto (OSOTF Excellence Award)
- Terry Fox Research Institute
- Canada Research Chairs
- Canada Foundation for Innovation (32383)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- circulating tumor DNA, pembrolizumab, immune checkpoint blockade, predictive biomarkers, solid tumors, ctDNA kinetics, ctDNA clearance, liquid biopsy, treatment response, progression-free survival, overall survival
- MeSH terms
- Circulating Tumor DNA, Humans, Neoplasms, Prospective Studies, Biomarkers, Antibodies, Monoclonal, Humanized
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