BackgroundProton pump inhibitors (PPIs) are reported to decrease the efficacy of immune checkpoint inhibitors (ICIs), but there are few reports on the association between ICI efficacy and antacids other than PPIs, and simultaneous examination of the effects of antacids, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) on ICI therapy. MethodsWe conducted a retrospective study of 381 patients with non-small cell lung cancer who received ICI therapy from January 1, 2016 to December 31, 2022. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Antacids included histamine type 2 receptor antagonists (H2RAs), PPIs, and potassium-competitive acid blockers (P-CABs). ResultsAntacids were administered to 218 patients, including 168 with PPIs, 37 with P-CABs, and 13 with H2RAs. Patients with antacids had worse median PFS and OS than those without antacids (PFS, 2.9 vs. 6.2 months; OS, 12.3 vs. 24.0 months), and those with PPIs, P-CABs, or H2RAs had similar results. However, there were no significant differences between patients with and without antacids when stratified by corticosteroid and NSAID use. Multivariate analyses showed that corticosteroids and NSAIDs administered for cancer-associated symptoms were related to poor prognosis, but antacids including PPIs, P-CABs, or H2RAs were not related. ConclusionsAntacids were not related to ICI efficacy when NSAIDs or corticosteroids were taken into consideration. This may be because the most frequent reason for administering NSAIDs and corticosteroids was cancer-associated symptoms, which are a poor prognostic factor, and most of the patients treated with these medications also received antacids.