Impact of Exposure to Benzodiazepines on Adverse Effects and Efficacy of PD-1/PD-L1 Blockade in Patients With Non-Small Cell Lung Cancer.

Abstract

Background: The impact of concomitant medications on immune-related adverse events (irAEs) and immune checkpoint inhibitor (ICI) efficacy in non-small cell lung cancer (NSCLC) remains unclear. Benzodiazepine receptor agonists (BZRAs), commonly prescribed for anxiety and insomnia in cancer care, may influence antitumor immunity via γ-aminobutyric acid (GABA) signaling. Here, we retrospectively analyzed medical records of NSCLC patients treated with ICIs.

Methods: In an initial exploratory analysis, BZRA use was significantly associated with a lower incidence of irAEs, prompting further evaluation. Propensity score matching (PSM) was performed to adjust for potential confounding factors. In the matched cohort, we assessed associations between BZRA use, irAE incidence, and ICI efficacy, as measured by progression-free survival (PFS) and overall survival (OS).

Results: In the matched cohort, BZRA use was significantly associated with a lower incidence of irAEs (OR 0.33, 95% CI: 0.13-0.80, p = 0.015). BZRA use was also linked to shorter PFS (HR 1.80, 95% CI: 1.13-2.86, p = 0.013), but not OS (HR 1.63, 95% CI: 0.95-2.81, p = 0.077). In subgroup analysis, among patients who developed irAEs, BZRA use was associated with shorter PFS (HR 2.69, 95% CI: 1.32-5.48, p = 0.007) and OS (HR 3.35, 95% CI: 1.40-8.04, p = 0.007), whereas no significant associations were observed in non-irAE patients.

Conclusion: BZRA use was associated with reduced irAE incidence and poorer ICI outcomes among patients who developed irAEs, suggesting potential immunosuppressive effects that may impair ICI efficacy in NSCLC.