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Impact of Exposure to Benzodiazepines on Adverse Effects and Efficacy of PD-1/PD-L1 Blockade in Patients With

Kiyoshi Takagaki1,2, Yoshiya Ohno1, Taiichiro Otsuki3,4

  • 1Laboratory of Immunobiology, School of Pharmacy, Hyogo Medical University, Kobe, Japan.

Thoracic Cancer
|May 14, 2025
PubMed
Abstract

Insights

Benzodiazepine receptor agonists (BZRAs) use in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) was linked to fewer immune-related adverse events (irAEs). However, BZRA use was also associated with worse outcomes, particularly in patients who experienced irAEs.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • The influence of concurrent medications on immune-related adverse events (irAEs) and immune checkpoint inhibitor (ICI) efficacy in non-small cell lung cancer (NSCLC) is not well understood.
  • Benzodiazepine receptor agonists (BZRAs), frequently used for anxiety and insomnia in cancer patients, may modulate antitumor immunity through GABA signaling pathways.

Purpose of the Study:

  • To investigate the association between benzodiazepine receptor agonist (BZRA) use and the incidence of irAEs and efficacy of ICIs in NSCLC patients.
  • To evaluate the impact of BZRAs on progression-free survival (PFS) and overall survival (OS) in NSCLC patients undergoing ICI therapy.

Main Methods:

  • Retrospective analysis of medical records from NSCLC patients treated with ICIs.
  • Propensity score matching (PSM) was employed to control for confounding variables.
  • Assessment of associations between BZRA use, irAE incidence, PFS, and OS in the matched cohort.

Main Results:

  • BZRA use was significantly associated with a lower incidence of irAEs (OR 0.33, p=0.015) in the matched cohort.
  • BZRA use was linked to shorter PFS (HR 1.80, p=0.013) but not significantly with OS (HR 1.63, p=0.077).
  • Among patients who experienced irAEs, BZRA use correlated with shorter PFS (HR 2.69, p=0.007) and OS (HR 3.35, p=0.007).

Conclusions:

  • BZRA use in NSCLC patients treated with ICIs is associated with reduced irAE incidence.
  • BZRA use may be linked to poorer ICI efficacy, particularly in patients who develop irAEs, suggesting potential immunosuppressive effects.
  • Further research is warranted to elucidate the mechanisms underlying BZRA's impact on ICI therapy outcomes.
Keywords:
benzodiazepinesconcomitant baseline medicationimmune checkpoint inhibitorsimmune‐related adverse eventsnon‐small cell lung cancer

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