Novel evidence for the prognostic impact of beta-blockers in solid cancer patients receiving immune checkpoint inhibitors

Objective: Cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has made encouraging achievements in both clinical trials and real-world studies. The beta-blockers, as common concomitant medications in clinical practice, have been suggested to exert anti-cancer effects in various human malignancies. This study aimed to clarify the prognostic impact of beta-blockers in solid cancer patients receiving ICI therapy.Method: A systematic literature review and meta-analysis was firstly performed based on databases including PubMed, Cochrane Library, Web of Science, Embase, and Clinicaltrials.gov before August 1th 2022. The asso-ciation of beta-blocker use with overall survival (OS) or progression-free survival (PFS) was determined using the hazard ratios (HRs) coupled with 95% confidence intervals (CIs). Then, a retrospective study enrolling 194 patients was performed to validate the results of the meta-analysis.Results: A total of 11 studies enrolling 10,156 patients were included in the meta-analysis. The pooled analysis demonstrated beta-blocker use was not significantly correlated with either OS (HR = 0.97(0.85-1.11)) or PFS (HR = 0.98(0.90-1.06)). Similar results were also observed in the subgroup analysis stratified by cancer type, age, sample size and ICI therapy, except for the OS (HR = 0.61(0.45-0.83)) and PFS (HR = 0.65(0.44-0.96)) in the studies with sample size less than 200. The retrospective study indicated no significant correlation between beta-blocker use and the clinical outcome in the entire cohort and lung cancer subgroup. However, beta-blocker use was found to be significantly associated with better objective response to ICI-based therapy in the entire cohort (odds ratio (OR) = 0.42(0.19-0.94), p = 0.036) and lung cancer subgroup (OR = 0.25(0.08-0.83), p = 0.024).Conclusion: Although both our up-to-date meta-analysis and retrospective study suggested beta-blocker use has no significant impact on the overall prognosis of solid cancer patients receiving ICIs, beta-blocker use may be associated with improved anti-cancer efficacy of ICIs. Considering study limitations, more clinical validations and mech-anism investigations are of great necessity for clarifying the role of beta-blockers in ICI-based therapy.