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Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study
Open accessAbstract
Background Recent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab and pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB.Patients and methods This prospective pilot study was conducted in patients with nonsmall cell lung cancer, uveal melanoma, or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie. ctDNA levels were assessed at baseline and after 8 weeks (w8) by bidirectional pyrophosphorolysis-activated polymerization, droplet digital PCR or next-generation sequencing depending on the mutation type. Radiological evaluation of efficacy of treatment was carried out by using immune-related response criteria.Results ctDNA was detected at baseline in 10 out of 15 patients. At w8, a significant correlation (r = 0.86; P = 0.002) was observed between synchronous changes in ctDNA levels and tumor size. Patients in whom ctDNA levels became undetectable at w8 presented a marked and lasting response to therapy. ctDNA detection at w8 was also a significant prognostic factor in terms of progression-free survival (hazard ratio = 10.2; 95% confidence interval 2.5-41, P < 0.001) and overall survival (hazard ratio = 15; 95% confidence interval 2.5-94.9, P = 0.004).Conclusion This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs.
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“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 KRAS G12C Predict Response to Adagrasib in KRAS Mutant Non–Small Cell Lung Cancer Patients (2023) · cites this paper as [16]
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Metadata
- Authors
- Cabel, L., Riva, F., Servois, V., Livartowski, A., Daniel, C., Rampanou, A., Lantz, O., Romano, E., Milder, M., Buecher, B., Piperno-Neumann, S., Bernard, V., Baulande, S., Bieche, I., Pierga, J. Y., Proudhon, C., & Bidard, F.-C.
- Affiliations
- Inserm (FR)
- Université Paris Descartes (FR)
- Université Paris-Saclay (FR)
- Corresponding author
- Bidard, F.-C.
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 28
- Issue
- 8
- Pages
- 1996-2001
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2607977201
- Cited by
- 315
- References
- 23
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 19 · 2023: 59 · 2022: 49 · 2021: 30 · 2020: 43 · 2019: 37 · 2018: 34 · 2017: 12
- FWCI
- 15.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-10-EQPX-0003)
- 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, liquid biopsy, anti-PD-1 therapy, immune checkpoint inhibitors, nivolumab, pembrolizumab, treatment response monitoring, non-small cell lung cancer, uveal melanoma, progression-free survival, overall survival, prognostic factors
- MeSH terms
- Aged, Aged, 80 and over, DNA, Neoplasm, Female, Humans, Immunotherapy, Male, Middle Aged, Monitoring, Physiologic, Neoplasms, Pilot Projects, Prognosis, Prospective Studies, Survival Analysis, Polymerase Chain Reaction, B7-H1 Antigen
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