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Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study

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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.·2017·Annals of Oncology

DOI 10.1093/annonc/mdx212

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Abstract

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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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: Cabel, L.
Riva, F.
Servois, V.
Livartowski, A.
Rampanou, A.
Lantz, O.
Romano, E.
Buecher, B.
Piperno-Neumann, S.
Baulande, S.
Pierga, J.Y.
Proudhon, C.
Bidard, F.-C.
Venue: Annals of Oncology
Publisher: Elsevier BV
Published: 2017-08
Volume: 28
Issue: 8
Pages: 1996-2001
ISSN: 0923-7534 (ISSN-L)
DOI: 10.1093/annonc/mdx212
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 889 d)
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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Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study

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