Systemic antibiotic exposure and outcomes of immune checkpoint inhibitors in non–small cell lung cancer.

Abstract

e20602 Background: Immune checkpoint inhibitors (ICIs) have transformed the management of solid tumors, particularly non–small cell lung cancer (NSCLC), yet durable benefit is achieved only in a subset of patients. The gut microbiota is a key modulator of antitumor immunity, and systemic antibiotic therapy (ABT), frequently prescribed in oncology, can disrupt microbial homeostasis. Observational studies suggest that ABT may impair ICI efficacy, but results remain heterogeneous, warranting an updated synthesis with tumor-specific analyses. Methods: We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. PubMed, Scopus, and EMBASE were searched for studies published between 2018 and 2025 evaluating the association between ABT exposure and time-to-event outcomes in patients with solid tumors treated with ICIs. Eligible studies reported a clearly defined ABT exposure window. Random-effects models were considered primary. A pre-specified sensitivity analysis focused on NSCLC, the largest and most methodologically homogeneous subgroup. Results: Fifteen studies encompassing 52,489 patients were included. Overall, ABT exposure was associated with worse overall survival (OS; random-effects HR 1.16, 95% CI 1.03–1.29) and numerically inferior progression-free survival (PFS; random-effects HR 1.11, 95% CI 0.95–1.27).In the NSCLC sensitivity analysis, 45,896 patients were analyzed. For OS, moderate heterogeneity was observed (I² = 51%), with a pooled fixed-effect HR of 1.05 (95% CI 0.996–1.11), indicating a consistent trend toward worse survival with ABT exposure. For PFS, no heterogeneity was detected (I² = 0%), and ABT exposure was associated with a significantly increased risk of disease progression (HR 1.16, 95% CI 1.02–1.30), with concordant fixed- and random-effects estimates. Conclusions: ABT administered in temporal proximity to ICIs is associated with inferior survival outcomes, with particularly robust and consistent evidence for worsened PFS in NSCLC. These findings support a microbiome-mediated impairment of immunotherapy efficacy and underscore the importance of cautious ABT stewardship in patients with NSCLC receiving ICIs. Prospective studies integrating microbiome profiling and standardized ABT exposure definitions are warranted.