The Impact of Beta Blockers on Survival Outcomes in Patients With Non-small-cell Lung Cancer Treated With Immune Checkpoint Inhibitors

Clin Lung Cancer. 2021 Jan;22(1):e57-e62. doi: 10.1016/j.cllc.2020.07.016. Epub 2020 Aug 5.

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 patients with lung cancer who concomitantly used beta blockers and immune checkpoint inhibitors (ICIs), with the hypothesis that beta blockade would positively impact clinical outcomes.

Patients and methods: We retrospectively reviewed the health records of 109 patients who were treated at Northwestern University from January 2014 through August 2018 with ICIs for non-small-cell lung cancer (NSCLC). Comparisons of overall survival 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 ICIs for NSCLC, 28 of them were concomitantly prescribed beta blockers. Use of beta blockers was associated with increased PFS, with a hazard ratio of 0.58 and 95% confidence interval of 0.36 to 0.93. There was not a significant increase in overall survival among patients who took beta blockers (hazard ratio, 0.66; 95% confidence interval, 0.38-1.17). In a regression model, beta blockers were identified as predictive of PFS, as were non-squamous histology, tumor programmed death-ligand 1 positivity, and lower line of treatment.

Conclusions: Our data suggests beta blocker use may be associated with improved PFS among patients treated with ICIs for NSCLC. This was a small study, and these findings should be further validated in prospective clinical studies.

Keywords: Adrenergic; Antidepressant; Immunotherapy; NSCLC; Stress response.

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / mortality*
  • Adenocarcinoma of Lung / pathology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Adrenergic beta-Antagonists
  • Immune Checkpoint Inhibitors