Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma
Abstract Background Efficacy of 2nd line treatment in advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma remains limited with no identified strong predictor of treatment efficacy. We evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting the efficacy of immune...
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Nature Portfolio
2025-04-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00867-x |
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| author | David Tougeron Christophe Louvet Jérôme Desramé Ludovic Evesque Antoine Angelergues Aurélien Carnot Gilles Breysacher Aziz Zaanan Nicolas Etchepare May Mabro Laure Kaluzinski Caroline Petorin Benoist Chibaudel Thomas Aparicio Anaïs Bodere Yves Rinaldi Karine Le Malicot Jean-François Emile Côme Lepage Aurélia Baures Hanane Djamai Valérie Taly Pierre Laurent-Puig |
| author_facet | David Tougeron Christophe Louvet Jérôme Desramé Ludovic Evesque Antoine Angelergues Aurélien Carnot Gilles Breysacher Aziz Zaanan Nicolas Etchepare May Mabro Laure Kaluzinski Caroline Petorin Benoist Chibaudel Thomas Aparicio Anaïs Bodere Yves Rinaldi Karine Le Malicot Jean-François Emile Côme Lepage Aurélia Baures Hanane Djamai Valérie Taly Pierre Laurent-Puig |
| author_sort | David Tougeron |
| collection | DOAJ |
| description | Abstract Background Efficacy of 2nd line treatment in advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma remains limited with no identified strong predictor of treatment efficacy. We evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting the efficacy of immune checkpoint inhibitors (ICI) plus chemotherapy in the randomized PRODIGE 59-FFCD 1707-DURIGAST trial. Methods ctDNA was evaluated before treatment (baseline) and at 4 weeks (before the third cycle of treatment, C3) using droplet-digital PCR assays based on the detection of CpG methylation. Results Progression-free survival (PFS) and overall survival (OS) were shorter in patients with a high (>1.1 ng/mL) versus low (<1.1 ng/mL) ctDNA concentration at baseline (2.3 vs. 5.8 months; HR = 2.19; 95% CI, 1.09–4.41; p = 0.03 and 4.5 vs. 12.9 months; HR = 2.73; 95% CI, 1.29–5.75; p < 0.01), respectively, after adjustment for identified prognostic variables. Patients with a ctDNA decrease ≤75% between baseline and C3 versus a ctDNA decrease >75% had a worse objective response rate (p = 0.007), shorter PFS (2.2 vs. 7.4 months, HR = 1.90; 95% CI, 1.03–3.51; p = 0.04) and OS (6.6 vs 16.0 months; HR = 2.18; 95% CI, 1.09–4.37; p = 0.03). Conclusions An early decrease in ctDNA concentration is a strong predictor of the therapeutic efficacy of ICI plus chemotherapy in advanced gastric/GEJ adenocarcinoma. Clinical Trial Information NCT03959293 (DURIGAST). |
| format | Article |
| id | doaj-art-c557335d45684d558830895da74d7b62 |
| institution | OA Journals |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| series | Communications Medicine |
| spelling | doaj-art-c557335d45684d558830895da74d7b622025-08-20T02:28:42ZengNature PortfolioCommunications Medicine2730-664X2025-04-015111110.1038/s43856-025-00867-xCirculating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinomaDavid Tougeron0Christophe Louvet1Jérôme Desramé2Ludovic Evesque3Antoine Angelergues4Aurélien Carnot5Gilles Breysacher6Aziz Zaanan7Nicolas Etchepare8May Mabro9Laure Kaluzinski10Caroline Petorin11Benoist Chibaudel12Thomas Aparicio13Anaïs Bodere14Yves Rinaldi15Karine Le Malicot16Jean-François Emile17Côme Lepage18Aurélia Baures19Hanane Djamai20Valérie Taly21Pierre Laurent-Puig22Department of Gastroenterology and Hepatology, Poitiers University HospitalDepartment of Medical Oncology, Institute Mutualiste MontsourisDepartment of Gastroenterology, Mermoz HospitalDepartment of Medical Oncology, Centre Antoine LacassagneDiaconesses Croix Simon HospitalDepartment of Gastroenterology and Digestive Oncology, Oscar Lambret CentreDepartment of Gastroenterology and Hepatology, Colmar HospitalDepartment of Digestive Oncology, Georges Pompidou European Hospital, AP-HP, Université Paris Cité, Paris Cancer Institute CARPEMDepartment of Gastroenterology, Valence HospitalDepartment of Oncology, Foch HospitalDepartment of Oncology, Cherbourg-en-Cotentin HospitalDepartment of Oncology, Clermont-Ferrand University HospitalDepartment of Oncology, Franco-Britannique Hospital – Fondation Cognacq-JayDepartment of Gastroenterology and Digestive Oncology, Saint Louis HospitalSaint Malo HospitalDepartment of Gastroenterology, Marseille European HospitalFédération Francophone de Cancérologie Digestive, EPICAD INSERM LNC-UMR 1231, Bourgogne Franche-Comté UniversityPathology Department, Paris-Saclay University, Versailles SQY University, EA4340-BECCOH, Assistance Publique–Hôpitaux de Paris (APHP), Ambroise-Paré HospitalFédération Francophone de Cancérologie Digestive, EPICAD INSERM LNC-UMR 1231, Bourgogne Franche-Comté UniversityCentre de recherche des cordeliers, Université Paris Cité, Sorbonne Université, UMR-S1138, CNRS SNC5096, Équipe Labélisée Ligue Nationale Contre le CancerCentre de recherche des cordeliers, Université Paris Cité, Sorbonne Université, UMR-S1138, CNRS SNC5096, Équipe Labélisée Ligue Nationale Contre le CancerCentre de recherche des cordeliers, Université Paris Cité, Sorbonne Université, UMR-S1138, CNRS SNC5096, Équipe Labélisée Ligue Nationale Contre le CancerCentre de recherche des cordeliers, Université Paris Cité, Sorbonne Université, UMR-S1138, CNRS SNC5096, Équipe Labélisée Ligue Nationale Contre le CancerAbstract Background Efficacy of 2nd line treatment in advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma remains limited with no identified strong predictor of treatment efficacy. We evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting the efficacy of immune checkpoint inhibitors (ICI) plus chemotherapy in the randomized PRODIGE 59-FFCD 1707-DURIGAST trial. Methods ctDNA was evaluated before treatment (baseline) and at 4 weeks (before the third cycle of treatment, C3) using droplet-digital PCR assays based on the detection of CpG methylation. Results Progression-free survival (PFS) and overall survival (OS) were shorter in patients with a high (>1.1 ng/mL) versus low (<1.1 ng/mL) ctDNA concentration at baseline (2.3 vs. 5.8 months; HR = 2.19; 95% CI, 1.09–4.41; p = 0.03 and 4.5 vs. 12.9 months; HR = 2.73; 95% CI, 1.29–5.75; p < 0.01), respectively, after adjustment for identified prognostic variables. Patients with a ctDNA decrease ≤75% between baseline and C3 versus a ctDNA decrease >75% had a worse objective response rate (p = 0.007), shorter PFS (2.2 vs. 7.4 months, HR = 1.90; 95% CI, 1.03–3.51; p = 0.04) and OS (6.6 vs 16.0 months; HR = 2.18; 95% CI, 1.09–4.37; p = 0.03). Conclusions An early decrease in ctDNA concentration is a strong predictor of the therapeutic efficacy of ICI plus chemotherapy in advanced gastric/GEJ adenocarcinoma. Clinical Trial Information NCT03959293 (DURIGAST).https://doi.org/10.1038/s43856-025-00867-x |
| spellingShingle | David Tougeron Christophe Louvet Jérôme Desramé Ludovic Evesque Antoine Angelergues Aurélien Carnot Gilles Breysacher Aziz Zaanan Nicolas Etchepare May Mabro Laure Kaluzinski Caroline Petorin Benoist Chibaudel Thomas Aparicio Anaïs Bodere Yves Rinaldi Karine Le Malicot Jean-François Emile Côme Lepage Aurélia Baures Hanane Djamai Valérie Taly Pierre Laurent-Puig Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma Communications Medicine |
| title | Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma |
| title_full | Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma |
| title_fullStr | Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma |
| title_full_unstemmed | Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma |
| title_short | Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma |
| title_sort | circulating tumor dna strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro esophageal adenocarcinoma |
| url | https://doi.org/10.1038/s43856-025-00867-x |
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