Association of β-blocker selectivity with survival and immune-related outcomes in melanoma and lung cancer patients treated with immune checkpoint inhibitors.

Abstract

11152 Background: Immune checkpoint inhibitors (ICIs) are standard of care for advanced melanoma and lung cancer. Retrospective studies suggest that non-selective β-blocker use correlates with improved overall survival, potentially through modulation of the tumor immune microenvironment. However, real-world evidence comparing the effect of selective versus non-selective beta-blockers remains limited. Methods: We conducted a multicenter retrospective study using the TriNetX Global Collaborative Network. Adult patients (≥18 years) with melanoma or lung cancer treated with immune checkpoint inhibitors (pembrolizumab, nivolumab, ipilimumab, atezolizumab, durvalumab, cemiplimab, or avelumab) were identified. Patients were categorized based on exposure to non-selective β-blockers (carvedilol, propranolol, nadolol, labetalol, timolol) or selective β-blockers (metoprolol, atenolol, bisoprolol, nebivolol, acebutolol) within two months before or at ICI initiation. The index date was first ICI exposure. One-to-one propensity score matching was performed using covariates selected based on baseline imbalance, including demographics, cardiovascular and cerebrovascular comorbidities, and prior procedures. The primary outcome was overall survival. Secondary outcomes included hospitalization and immune-related adverse events (irAEs), defined using a composite endpoint of organ-specific immune-mediated toxicities based on prior published methodology. Results: After matching, 3,720 patients with melanoma and 11,160 patients with lung cancer were included in the analysis. Among melanoma patients treated with ICIs, non-selective β-blocker use was associated with lower mortality (HR 0.799; 95% CI 0.652–0.980) and decreased hospitalization (HR 0.865; 95% CI 0.759–0.984) compared with selective β-blockers. Most immune-related adverse events did not differ between groups, except for higher hepatic toxicity with non-selective β-blockers (HR 1.382; 95% CI 1.064–1.796). In lung cancer patients, non-selective β-blocker use was associated with lower mortality (HR 0.847; 95% CI 0.797–0.900), reduced ICU admission (HR 0.87; 95% CI 0.800–0.946), and decreased hospitalization (HR 0.912; 95% CI 0.864–0.963). Additionally, fewer cardiovascular (RR 0.811; 95% CI 0.711–0.925) and respiratory (RR 0.842; 95% CI 0.772–0.918) immune-related adverse events compared with selective β-blockers. Conclusions: In this real-world, propensity-matched analysis, non-selective β-blocker use was associated with improved early survival and reduced healthcare utilization among melanoma and lung cancer patients treated with ICIs. These findings suggest that non-selective β-blockers represent a low-cost and available adjunct to immunotherapy and warrants prospective validation.