Gut Dysbiosis as a Potential Guide for Immunotherapy (Dis)Continuation After 2 Years in NSCLC - A Brief Report

Sep 29, 2026

Phase III trials set 2 years as the standard duration of immune checkpoint blockers (ICB) for advanced NSCLC, yet criteria for safely discontinuing ICB remain unclear. Evidence links ICB outcomes to gut microbiota, supporting gut microbial taxonomic profiling as a biomarker to guide treatment decisions. A retrospective analysis evaluated clinical outcomes and the utility of multiomic decision-making tools in NSCLC patients who completed 24 months of ICB-based therapy without disease progression.

LanguageEnglish

CategoryResearch & Report

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Pages7

Reading Time18 min

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Abstract

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Introduction

BRIEF REPORT Gut Dysbiosis as a Potential Guide for Immunotherapy (Dis)Continuation After 2 Years in NSCLC: A Brief Report Adele Bonato, MD,a,b,c,d Claudia Parisi, MD,a,b,e Priscilla Cascetta, MD,a,b,f Anna Reni, MD,a,b,c,g May-Lucie Meyer, MD,a,b,h Mariona Riudavets, MD, PhD,a,b David Planchard, MD, PhD,a,b Benjamin Besse, MD, PhD,a,b Jordi Remon, MD,a,b Francesco Facchinetti, MD, PhD,a,b Lorenzo Belluomini, MD, PhD,a,b,c,g,* Lisa Derosa, MD, PhD,a,b,c,d Fabrice Barlesi, MD, PhDa,b aDepartment of Cancer Medicine, Gustave Roussy Cancer Medicine, Villejuif, France bDepartment of Cancer Medicine, Paris-Saclay University, Ile-de-France, France cClinicObiome, Institut National De La Santé Et De La Recherche Médicale (INSERM) U1015, Gustave Roussy Cancer Campus, Villejuif, France dMedical Oncology Department, Azienda Ospedaliero Universitaria (AOU) Pisana–Stabilimento di Santa Chiara, Pisa, Italy eDepartment of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University, Rome, Italy fMedical Oncology Division, Cliniche Humanitas Gavazzeni, Bergamo, Italy gSection of Innovation Biomedicine–Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona, Italy hDepartment of Oncology, Centre Hospitalier Universitarie Vaudois, Lausanne University, Lausanne, Switzerland Received 6 June 2025; revised 21 October 2025; accepted 23 October 2025 Available online -29 October 2025 ABSTRACT Background: Although most phase III pivotal trials have set the duration of immune checkpoint blockers (ICB) for advanced NSCLC at 2 years, the criteria for safely discontinuing ICB remain undefined. Growing evidence links ICB efficacy to gut microbiota, positioning gut microbial taxonomic profiling as a promising biomarker to guide treatment decisions. We performed a retrospective analysis exploring clinical outcomes and the utility of multiomic decision-making tools in patients with NSCLC at Gustave Roussy who completed 24 months of ICB-based therapy without disease progression (PD) . Methods: Patients receiving ICB between July 2016 and January 2023 were identified from the ONCOBIOTICS (NCT04567446) and STING (NCT04932525) study datasets. We selected those who reached 24 months of treatment without disease progression. Clinical characteristics and multiomic assessments, including gut microbiota profiling (TOPOSCORE by whole-genome sequencing), positron emission tomography–18-fluorodeoxyglucose imaging, and circulating tumor DNA, collected at 24 months, were analyzed. Key outcomes included overall survival (OS), progression-free survival (PFS), and PFS rates at 24 months after the completion of 2 years of ICB, stratified by molecular, metabolic, and microbial signatures. Results: Out of 123 patients treated for at least 18 months, 35 completed 24 months, with 31 eligible for the analysis. Of these, 68% continued ICB, whereas 32% discontinued therapy at the physician’s decision. Clinical characteristics were similar across groups. After a median follow-up of 59.1 months, OS and PFS did not differ significantly between those who discontinued and those who continued treatment *Corresponding author. Drs. Bonato and Parisi share first co-authorship and equally contributed to this work. Drs. Belluomini, Derosa, and Barlesi are senior authors. Address for correspondence: Lorenzo Belluomini, MD, PhD, Section of Innovation Biomedicine–Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona, P. le L.A. Scuro 10, Verona 37134, Italy. E-mail: [lorenzo.belluomini@univr.it](lorenzo.belluomini@univr.it) [Cite this article as: Bonato A](Cite this article as: Bonato A), Parisi C, Cascetta P, et al. Gut dysbiosis asa potential guide for immunotherapy (dis)continuation after 2 years in NSCLC: a brief report. JTO Clin Res Rep 2026;7:100928 . © 2025 The Authors. Published by Elsevier Inc. on behalf of the Internatio

FAQs

Why is discontinuing immune checkpoint blockers after 2 years in NSCLC still debated?

Most pivotal trials use a fixed 2-year duration, but the criteria for safely stopping ICB have not been defined. Clinicians remain cautious due to ongoing uncertainty about fixed-duration versus continuous treatment.

What data and patients were analyzed in the study?

Patients receiving ICB between July 2016 and January 2023 were identified from ONCOBIOTICS and STING study datasets, and those reaching 24 months without disease progression were selected. Gut microbiota profiling, PET-18F-FDG imaging, and circulating tumor DNA were assessed at 24 months.

What were the key findings regarding survival after stopping versus continuing ICB?

Overall survival and progression-free survival did not differ significantly between patients who discontinued and those who continued ICB after 2 years. Gut microbiota composition showed a trend toward association with PFS rates, with more favorable microbiota profiles linked to higher sustained response at 24 months.

Sep 29, 2026

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