The Efficacy and Safety of Beta-blockers and Immune Checkpoint Inhibitors in Patients with Cancer: A Systematic Review and Meta-analysis
Kota Tokunaga, Yu Fujiwara, Reo Omori, Takumi Sato, Manmeet S. Ahluwalia, Sarbajit Mukherjee
Abstract
Immune checkpoint inhibitors (ICIs) are now standard for various cancers, and preclinical studies suggest beta-blockers (BBs) may boost the efficacy of ICIs. However, prior clinical studies had small sample sizes, requiring large-scale validation. We aimed to evaluate the efficacy and safety of combining BBs with ICIs in patients with solid tumors through a systematic review and meta-analysis. A systematic search of PubMed/MEDLINE and Embase was conducted for studies on BBs plus ICIs for solid tumors up to July 2024. Outcomes of interest were overall survival, progression-free survival, and adverse events. Hazard ratios with 95% confidence intervals were pooled using a random-effects model meta-analysis, with heterogeneity assessed by I 2 statistics. Overall, 12 clinical studies involving 4293 patients with solid tumors were included, with 1463 patients receiving both BBs and ICIs and 2830 patients receiving ICIs alone. The combination of BBs and ICIs was not associated with a longer overall survival (hazard ratio 1.02; 95% confidence interval 0.84–1.23; p = 0.87; I 2 = 69%) or progression-free survival (hazard ratio 0.98; 95% confidence interval 0.80–1.20; p = 0.81; I 2 = 71%). Subgroup analyses by cancer types and BB types showed no significant heterogeneity in the hazard ratios for overall survival across different cancer types ( I 2 = 0%, p for heterogeneity = 0.44) and BB types ( I 2 = 0%, p for heterogeneity = 0.67). The combination of BBs plus ICIs did not seem to increase toxicity. Despite positive preclinical findings, this meta-analysis showed that adding BBs to ICIs was not associated with longer survival. We await the results of ongoing prospective trials assessing this strategy. CRD42024574043.