{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:21:33Z","timestamp":1792027293022,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K11360"],"award-info":[{"award-number":["24K11360"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Emerging evidence indicates that baseline use of certain concomitant drugs may affect the efficacy of immune checkpoint inhibitors (ICIs), including PD\u20101, PD\u2010L1, and CTLA\u20104 inhibitors, in patients with cancer. However, most previous studies have evaluated individual drug classes in isolation, without considering potential interactions among multiple drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aimed to evaluate the individual and combined effects of commonly prescribed concomitant drugs on the efficacy and safety of ICI\u2010based therapy in patients with non\u2010small cell lung cancer (NSCLC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective analysis of 124 patients with advanced or recurrent NSCLC who received first\u2010line ICI\u2010based treatments at a single institution. Drug exposure at treatment initiation was assessed for proton pump inhibitors (PPIs), low\u2010dose aspirin, non\u2010steroidal anti\u2010inflammatory drugs, statins, biguanides, antibiotics, and probiotics. Associations with progression\u2010free survival (PFS), overall survival (OS), and immune\u2010related adverse events (irAEs) were analyzed using multivariate Cox regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PPI use was independently associated with shorter PFS (HR: 2.44,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and OS (HR: 2.04,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01). In contrast, low\u2010dose aspirin use was independently associated with longer PFS (HR: 0.31,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01). Patients receiving both PPIs and aspirin had longer PFS and OS compared to those receiving PPIs alone, although the differences were not statistically significant. No consistent associations were observed for other drugs. The incidence of irAEs was not significantly affected by concomitant drug use.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PPI use at baseline may be associated with reduced efficacy of ICI therapy in NSCLC patients. In contrast, low\u2010dose aspirin use was independently associated with improved PFS, and may potentially mitigate the negative effects of PPIs. These findings underscore the importance of considering concomitant drug use when initiating ICI treatment. Prospective studies are needed to validate these observations and clarify underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70399","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T11:14:43Z","timestamp":1762427683000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of the Combination of Concomitant Drugs on Efficacy of Immune Checkpoint Inhibitors in Non\u2010Small Cell Lung Cancer"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6617-0991","authenticated-orcid":false,"given":"Masafumi","family":"Saiki","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medicine University of Yamanashi  Chuo Yamanashi 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8128-4839","authenticated-orcid":false,"given":"Tsukasa","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medicine University of Yamanashi  Chuo Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8977-3748","authenticated-orcid":false,"given":"Satoshi","family":"Furuya","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medicine University of Yamanashi  Chuo Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So","family":"Shimamura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medicine University of Yamanashi  Chuo Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisa","family":"Omori","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medicine University of Yamanashi  Chuo Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5500-2903","authenticated-orcid":false,"given":"Hiroki","family":"Ohkoshi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medicine University of Yamanashi  Chuo Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6778-2764","authenticated-orcid":false,"given":"Yuki","family":"Hoshino","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medicine University of Yamanashi  Chuo Yamanashi 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