Impact of antibiotic use on survival in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitor and chemotherapy

Int J Clin Oncol. 2025 Nov;30(11):2277-2286. doi: 10.1007/s10147-025-02860-9. Epub 2025 Aug 28.

Abstract

Background: Evidence suggests that antibiotic (ATB) use may negatively impact the efficacy of immune checkpoint inhibitors (ICIs) in treating advanced non-small cell lung cancer (NSCLC). We previously demonstrated that ATB use was significantly associated with decreased survival in NSCLC patients receiving ICI monotherapy. This study aimed to investigate the effect of ATB use on survival in NSCLC patients undergoing combined ICI and chemotherapy.

Patients and methods: We evaluated the impact of ATB on survival in NSCLC patients treated with ICIs and chemotherapy in this multicenter retrospective study. We analyzed outcomes such as progression-free survival (PFS) and overall survival (OS) in patients who received ATB within 2 months before or 1 month after starting ICI and chemotherapy combination therapy.

Results: Among 451 patients, 113 received ATB (ATB group) and 338 did not (ATB-unexposed). The median PFS was 7.1 months in the ATB group and 8.4 months in the ATB-unexposed group. The median OS was 18.0 months in the ATB group compared to 23.8 months in the ATB-unexposed group, indicating a significant reduction in both PFS and OS for the ATB group. Notably, this negative impact was not observed in patients who used probiotics (PFS: 6.0 vs. 7.6 months, p = 0.355; OS: 16.7 months vs. not reached (NR), p = 0.179).

Conclusion: ATB use was significantly associated with poorer survival outcomes in NSCLC patients treated with combined ICI and chemotherapy, but this effect was attenuated by probiotics.

Keywords: Antibiotics; Chemotherapy; Immune checkpoint inhibitor; PD-1 antibody; PD-L1 antibody.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / adverse effects
  • Anti-Bacterial Agents* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / administration & dosage
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Retrospective Studies

Substances

  • Immune Checkpoint Inhibitors
  • Anti-Bacterial Agents