Prognostic role of selective beta-1 blockers in patients treated with immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and prognosis. Beta-adrenergic activation contributes to cancer initiation and progression. While non-selective beta-blockers were found to improve the efficacy of ICIs therapy, the role of beta-1 (β1)-selective beta-blocker (β₁B) is unknown. We aimed to evaluate the association between baseline selective β1-blocker therapy and all-cause mortality and cardiovascular immune-related adverse events (CV irAEs) among patients treated with ICIs.

We performed a retrospective single-center study including patients diagnosed with cancer and treated with ICIs therapy.

Among 2409 patients, 591 (25%) were pretreated with β₁B. Patients in the β₁B group were older (72 ± 9 vs. 64 ± 13 years, p < 0.001) with a higher prevalence of cardiac risk factors and CV diseases including ischemic heart disease (40% vs. 8%, p < 0.001), heart failure (HF) (9% vs. 2%, p < 0.001) and atrial fibrillation (AF) (15% vs. 3%, p < 0.001). Patients pretreated with β₁B showed significantly increased all-cause mortality (68% vs. 57%, p < 0.001) and CV irAEs (14% vs. 7%, p < 0.001), mainly HF (7% vs. 3%, p < 0.001) and AF (7% vs. 3%, p < 0.001). In a multivariate analysis, β₁B remained a strong independent predictor for all-cause mortality (Hazard Ratio (HR) 1.21 [95% CI 1.05-1.39]), p = 0.010), however, not for CV irAEs (HR 1.22 [95% CI = 0.84-1.77], p = 0.290). The association between baseline selective β1-blocker treatment and increased all-cause mortality was consistent among patients with or without baseline CV disease.

Baseline β₁B therapy may be an independent predictor of increased all-cause mortality in patients treated with ICIs.