20.500.12556/RUL-179608 Timing and intensity of proton pump inhibitor exposure hampers overall survival in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors a retrospective cohort study Introduction: Proton pump inhibitor (PPI) use has been associated with reduced immune checkpoint inhibitor (ICI) efficacy in metastatic non-small cell lung cancer (mNSCLC) with evidence limited to their use during a short time period around ICI initiation. This study evaluated the associations between the timing and intensity of PPI exposure up to one year before ICI initiation and overall survival (OS) in mNSCLC patients treated with ICIs. Methods: This retrospective cohort study included consecutive mNSCLC patients treated with ICIs within routine clinical practice. Patients were grouped by the timing of PPI exposure from 365 days before to 30 days after (−365 to +30 days) ICI initiation: (1) no PPIs within −365 to +30 days; (2) PPIs only within −365 to −31 days; and (3) PPIs also within ±30 days of ICI initiation. The intensity of PPI exposure was quantified with the total defined daily doses (DDDs). OS was estimated using Kaplan–Meier methods, and associations between PPI exposure and OS were analyzed using Cox proportional hazards models. Results: Of 391 patients included (median age 64.7 years, 58.6% male), 73.4% had access to PPI within −365 to +30 days of ICI initiation. PPI exposure within ±30 days (220 patients) was associated with reduced median OS (mOS) compared with no PPI exposure between −365 and +30 days of ICI initiation (mOS 15.4 vs 21.9 months; adjusted hazard ratio [aHR] 1.373, 95% CI 1.007–1.873, p = 0.045). High-intensity PPI exposure within −365 to +30 days of ICI initiation (DDD > 159; 108 patients) was also associated with reduced mOS compared with no PPI exposure in this period (mOS 13.4 vs 21.9 months; aHR 1.454, 95% CI 1.023–2.067, p = 0.037). Discussion: PPI use around ICI initiation as well as PPI treatment intensity over a wider period was associated with reduced OS. Efforts should be made to streamline PPI use. carcinoma non-small-cell lung immune checkpoint inhibitors proton pump inhibitors survival analysis gastrointestinal microbiome karcinom nedrobnocelična pljuča zaviralci imunskih kontrolnih točk zaviralci protonske črpalke analiza preživetja gastrointestinalni mikrobiom rak (medicina) nedrobnocelični pljučni rak true false true Angleški jezik Slovenski jezik Članek v reviji 2026-02-18 10:23:32 2026-02-18 10:23:38 2026-02-19 04:39:46 0000-00-00 00:00:00 2026 0 0 Str. 1-13 Vol. 17, art, 1682723 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.24-006 1664-3224 10.3389/fimmu.2026.1682723 266366979 fimmu-17-1682723.pdf fimmu-17-1682723.pdf 1 4603D7FA1E32D08C4CE5402B519F5CD9 69ff2ad6ee9ec00b8ffd8a24d2ddc382302a266fa8269a875234c9051ff95631 c4e452cf-0cab-11f1-a1ba-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=228338 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1682723/full 1 44eff77b-0cab-11f1-a1ba-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=228337 Fakulteta za farmacijo 0 0 0