{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:21:30Z","timestamp":1792027290638,"version":"4.4.0"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Immune checkpoint inhibitors (ICIs) improve survival in advanced non-small-cell lung cancer (NSCLC), yet treatment responses vary. The potential influence of proton pump inhibitors (PPIs), metformin, statins, and nonsteroidal anti-inflammatory drugs (NSAIDs) on immunotherapy efficacy has gained increasing attention. This study aimed to evaluate the associations of these medications with survival outcomes. Materials and Methods: This retrospective cohort study included 179 patients with advanced NSCLC who received second-line nivolumab. The use of PPIs, metformin, statins, and NSAIDs was assessed within a \u00b130-day exposure window around nivolumab initiation. Sensitivity analyses were performed including all four studied medications. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan\u2013Meier method and Cox regression models. Results: Median follow-up was 19 months, and 52.5% of patients used PPIs. In univariable analysis, PPI use was significantly associated with worse PFS (HR = 2.01; p &lt; 0.001), while PD-L1 \u2265 50% expression was associated with improved PFS (HR = 0.57; p = 0.034). In multivariable analysis, PPI use remained independently associated with worse PFS (HR = 2.22; p &lt; 0.001), and male sex was associated with improved PFS (HR = 0.56; p = 0.013). For OS, PPI use (HR = 1.53; p = 0.043), ECOG \u2265 2 (HR = 2.09; p = 0.001), and male sex (HR = 0.53; p = 0.008) were significant factors in univariable analysis. In multivariable analysis, PPI use (HR = 2.01; p = 0.002) and ECOG \u2265 2 (HR = 2.21; p = 0.001) were independent adverse prognostic factors, while male sex was independently associated with improved OS (HR = 0.41; p = 0.001). Median PFS was 5 months in PPI users versus 9 months in non-users (p &lt; 0.001); median OS was 9 versus 14 months (p = 0.036). The use of metformin, statins, and NSAIDs showed no significant relationship with PFS or OS. Sensitivity analyses supported an association between PPI use and worse outcomes. Conclusions: PPI use was associated with worse PFS and OS in patients with advanced NSCLC receiving second-line nivolumab. These findings suggest that unnecessary PPI use should be carefully reassessed during immunotherapy.<\/jats:p>","DOI":"10.3390\/medicina62071413","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:35:52Z","timestamp":1784630152000},"page":"1413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proton Pump Inhibitor Use and Survival Outcomes in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Immunotherapy: A Real-World Study"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-1606","authenticated-orcid":false,"given":"Salih","family":"Karatl\u0131","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Etlik City Hospital, 06010 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-507X","authenticated-orcid":false,"given":"Seher","family":"Kaya","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Etlik City Hospital, 06010 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5678-2633","authenticated-orcid":false,"given":"Selahattin","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Etlik City Hospital, 06010 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0333-1388","authenticated-orcid":false,"given":"Ay\u015feg\u00fcl","family":"\u0130lhan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Etlik City Hospital, 06010 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4139-067X","authenticated-orcid":false,"given":"\u00d6zgen Ahmet","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Etlik City Hospital, 06010 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3713","DOI":"10.1158\/1078-0432.CCR-15-2998","article-title":"Nivolumab and Pembrolizumab for Non-Small Cell Lung Cancer","volume":"22","author":"Morgensztern","year":"2016","journal-title":"Clin. 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