Differential impact of proton pump inhibitors and antibiotics on immunotherapy efficacy after chemoradiotherapy in locally advanced non-small-cell lung cancer: a post-hoc analysis of the PACIFIC trial

作者：Leonardo Brunetti, Valentina Santo, David J Pinato, Fabrizio Citarella, Sarah Orlando, Fabian Acker, Vittoria Colella, Biagio Ricciuti, Jarushka Naidoo, Amin Nassar, Heather A. Wakelee, Kazuki Takada, Abdul Rafeh Naqash, Marina Chiara Garassino, Carlo Greco, Sara Ramella, Francesco Pantano, Giuseppe Tonini, Bruno Vincenzi, B.T. Arlunno, Jordi Remon, Claudia Parisi, David Planchard, Benjamin Besse, Antoine Desilets, Bertrand Routy, Arielle Elkrief, Fabrice Barlési, Lisa Derosa, Alessio Cortellini · 发表于：The Lancet Oncology · 年份：2026 · DOI：10.1016/s1470-2045(26)00191-9 · 研究领域：Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers、Cancer Research and Treatments

BACKGROUND: Baseline exposure to antibiotics and proton pump inhibitors has been associated with reduced efficacy of immune checkpoint inhibitors in patients with advanced tumours, possibly through gut microbiome disruption. Whether this outcome extends to those with earlier-stage disease remains unclear. We aimed to assess the association of baseline antibiotics and proton pump inhibitors with progression-free survival and overall survival in patients with unresectable stage III non-small cell lung cancer (NSCLC). METHODS: PACIFIC was a randomised, double-blind, placebo-controlled phase 3 trial done in patients aged 18 years or older with unresectable stage III squamous or non-squamous NSCLC, WHO performance status 0-1, and no progression after two or more cycles of concurrent chemoradiotherapy. Patients were randomly assigned (2:1) to durvalumab 10 mg/kg intravenously every 2 weeks for up to 12 months or placebo, starting 1-42 days after chemoradiotherapy; patients were stratified by age, sex, and smoking history. This post-hoc analysis was based on the final 5-year data cutoff date of the completed trial and included the treated population with consent for exploratory analyses. Co-primary endpoints were progression-free survival and overall survival, assessed according to baseline exposure to proton pump inhibitors and systemic antibiotics. This trial is registered on ClinicalTrials.gov (NCT02125461). FINDINGS: Between May 9, 2014, and April 22, 2016, 713 patients were ran...