Co-medications and gut microbiome in NSCLC immunotherapy
Mené sur 713 patients ayant reçu au moins 2 cycles de chimioradiothérapie pour un cancer du poumon non à petites cellules de stade III non résécable (durée médiane de suivi : 62,4 mois ; 68,6 % d'hommes), cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, du durvalumab en fonction de l'exposition initiale aux antibiotiques et/ou aux inhibiteurs de la pompe à protons
In a post-hoc analysis of the PACIFIC trial published in The Lancet Oncology, Leonardo Brunetti and colleagues1 found that baseline proton pump inhibitor and antibiotic use was associated with worse progression-free survival in patients with stage III non-small-cell lung cancer (NSCLC) treated with durvalumab after chemoradiotherapy, but not in those treated with placebo. This treatment-specific effect suggests an interaction with immunotherapy that is potentially mediated by microbiome disruption. An exploratory cohort also showed that baseline gut dysbiosis, measured by the Toposcore metric, was associated with shorter progression-free survival.1 These findings expand on the growing literature linking microbiome-disrupting medications to impaired outcomes from immune checkpoint inhibitors in advanced disease; meta-analyses consistently report associations with worse progression-free and overall survival with the use of antibiotics and proton pump inhibitors, although most studies are retrospective, variably define exposure windows, and do not have appropriate negative control groups.
The Lancet Oncology , commentaire, 2026