The impact of beta blockers on survival outcomes in non-small cell lung cancer patients treated with immune checkpoint inhibitors

Abstract Background Beta blockers have been associated with anti-tumorigenic effects, potentially by reducing adrenergic-mediated stress responses. Preclinical studies have additionally shown that beta blockade may enhance the efficacy of cancer immunotherapy. We investigated lung cancer patients who concomitantly used beta blockers and immune checkpoint inhibitors, with the hypothesis that beta blockade would positively impact clinical outcomes. Methods We retrospectively reviewed the health records of 109 patients who were treated at Northwestern University between January 2014 through August 2018 with immune checkpoint inhibitors for non-small cell lung cancer (NSCLC). Comparisons of overall survival (OS) and progression-free survival (PFS) were performed using Kaplan-Meier analysis with log-rank test, and a univariate regression analysis was performed with a Cox proportional hazards model Results Among 109 patients treated with immune checkpoint inhibitors for NSCLC, 28 of them were concomitantly prescribed beta blockers. Use of beta blockers was associated with increased PFS, with hazard ratio (HR) of 0.58 and 95% confidence interval (CI) of 0.36-0.93. There was not a significant increase in overall survival (OS) among patients who took beta blockers (HR 0.66, 95% CI 0.38-1.17). In a regression model, beta blockers were identified as predictive of PFS, as were non-squamous histology, tumor PD-L1 positivity, and lower line of treatment. Conclusions Our data suggests beta blocker use may be associated with improved PFS among patients treated with immune checkpoint inhibitors for NSCLC. This was a small study and these findings should be further validated in prospective clinical studies.