Impact of medications on the efficacy of immune checkpoint inhibitors in patients with recurrent or metastatic head and neck cancer

Jun 4, 2025International journal of clinical oncology

How Medications Affect Immune Therapy Success in Recurrent or Spread Head and Neck Cancer

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Abstract

Antibiotic administration within 60 days before immune checkpoint inhibitor initiation was associated with worse overall survival, with a median of 11.9 months compared to 20.5 months without antibiotics.

Worse overall survival was observed in patients who received antibiotics prior to treatment compared to those who did not.
Patients treated with antibiotics had a median progression-free survival of 3.0 months, significantly lower than the 5.8 months for those without antibiotics.
Tetracycline antibiotics were found to be particularly harmful to survival outcomes.
No significant differences in overall survival or progression-free survival were noted for patients taking proton pump inhibitors or statins.
Overall response rate and disease control rate showed no significant associations with the use of antibiotics, proton pump inhibitors, or statins.

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BACKGROUND: Immune checkpoint inhibitors (ICIs) are standard treatments for recurrent or metastatic head and neck cancer (RM-HNC). However, variability in treatment response necessitates the exploration of predictive factors, including gut microbiota, which are influenced by antibiotics, proton pump inhibitors (PPIs), and statins. This retrospective study assessed the effects of these medications on the clinical outcomes of ICI-treated patients with RM-HNC.

METHODS: This retrospective cohort study included 112 patients with RM-HNC who received nivolumab or pembrolizumab monotherapy between 2017 and 2022 at Nagoya City University Hospital. The effects of medications on overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were evaluated using the Kaplan-Meier method and Cox proportional hazards model.

RESULTS: Antibiotic administration within 60 days before ICI initiation was significantly associated with worse OS (median OS, 11.9 vs 20.5 months, p = 0.011) and PFS (median PFS, 3.0 vs 5.8 months, p = 0.018). Subgroup analyses indicated that tetracyclines were particularly detrimental. No significant differences in OS or PFS were observed with PPI or statin administration, and no significant associations of ORR or DCR were detected with antibiotic, PPI, or statin administration.

CONCLUSION: Antibiotic administration was associated with worse survival in patients with RM-HNC receiving ICIs. These findings underscore the need for careful consideration of antibiotic administration in patients undergoing ICI therapy and highlight the importance of further research to optimize treatment strategies.

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Impact of medications on the efficacy of immune checkpoint inhibitors in patients with recurrent or metastatic head and neck cancer

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