Background: The introduction of immunotherapy has significantly improved survival outcomes in many solid tumors. However, a subset of patients exhibits limited responsiveness to immune checkpoint inhibitors (ICIs). Emerging evidence indicates that the gut microbiota plays a critical role in modulating the effectiveness of immunotherapy. Consequently, the concurrent use of certain medications that disrupt microbial diversity may contribute to reduced treatment efficacy. Among the agents implicated in altering the gut microbiota are antibiotics and proton pump inhibitors (PPIs).Methods: A systematic literature search was conducted in PubMed, Scopus, and EMBASE. Eligible studies assessed the association between PPI use and progression-free survival (PFS) and/or overall survival (OS) in patients with solid tumors receiving ICIs. They reported hazard ratios (HRs) with 95% confidence intervals (CIs). The analysis focused on studies published between November 2022 and January 2025, in continuity with prior comprehensive meta-analyses that included studies up to November 2022. This contiguity-based approach enabled a focused evaluation of recent evidence, minimizing redundancy while allowing for the detection of evolving trends in clinical practice and methodology. Data were synthesized using both fixed-effects and random-effects models and visualized via Forest plots. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) and the Newcastle–Ottawa Scale (NOS). Between-study heterogeneity and publication bias were evaluated using I2statistics and funnel plots.Results: From a pool of over 400 screened articles between November 2022 and January 2025, seven studies met the inclusion criteria. The PFS analysis incorporated data from 1367 participants, while the OS analysis included 10,420 individuals. Use of PPIs was linked to a 12% higher risk of disease progression (HR = 1.12; 95% CI: 0.90–1.34) and an 18% increased mortality risk (HR = 1.18; 95% CI: 1.11–1.25).Conclusions: The observed association between PPIs exposure and reduced efficacy of ICIs, as reflected in worsened PFS and OS outcomes, highlights a potential clinical concern that merits further investigation in prospective studies.
背景：免疫疗法的引入显著改善了许多实体瘤患者的生存结局。然而，部分患者对免疫检查点抑制剂（ICIs）的反应有限。新近证据表明，肠道微生物群在调节免疫治疗效果中起着关键作用。因此，同时使用某些破坏微生物多样性的药物可能导致疗效降低。其中，抗生素和质子泵抑制剂（PPIs）被认为会改变肠道微生物群。 方法：在PubMed、Scopus和EMBASE数据库中进行系统性文献检索。符合条件的研究评估了在接受ICIs治疗的实体瘤患者中，使用PPIs与无进展生存期（PFS）和/或总生存期（OS）之间的关联，并报告了风险比（HRs）及其95%置信区间（CIs）。分析聚焦于2022年11月至2025年1月期间发表的研究，以延续先前涵盖至2022年11月研究的全面荟萃分析。这种基于连续性的方法能够集中评估近期证据，在最大限度减少重复的同时，有助于发现临床实践和方法学上的演变趋势。数据采用固定效应和随机效应模型进行综合，并通过森林图可视化。研究质量使用非随机研究方法学指数（MINORS）和纽卡斯尔-渥太华量表（NOS）进行评估。研究间异质性和发表偏倚分别通过I²统计量和漏斗图进行评估。 结果：从2022年11月至2025年1月期间筛选的400多篇文章中，七项研究符合纳入标准。PFS分析纳入了1367名参与者的数据，而OS分析则包括了10,420名个体。使用PPIs与疾病进展风险增加12%（HR = 1.12；95% CI：0.90–1.34）以及死亡风险增加18%（HR = 1.18；95% CI：1.11–1.25）相关。 结论：观察到的PPIs暴露与ICIs疗效降低之间的关联，体现在恶化的PFS和OS结局上，突显了一个值得在前瞻性研究中进一步探讨的潜在临床问题。
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