The oral administration of beta blockers (β-blockers) in a cohort of patients with resected high-risk melanoma who received pembrolizumab or placebo in the KEYNOTE-054 trial had no independent prognostic effect on recurrence-free survival (RFS). However, β-blockers may increase the efficacy of pembrolizumab.

“β-adrenergic receptors are upregulated in melanoma cells and contribute to an immunosuppressive, pro-tumorigenic microenvironment,” wrote lead author Oliver Kennedy, MD, PhD, University of Manchester, United Kingdom, and co-authors.

In the phase 3 KEYNOTE-054 trial, 1019 patients with resected, stage 3 melanoma were randomized to either 200 mg of adjuvant pembrolizumab or placebo every 3 weeks for 1 year or until recurrence or unacceptable toxicity. A total of 99 (10%) of patients received oral β-blockers within 30 day of randomization. Cox proportional hazard model was used to estimate the hazard ratio (HR) for the association between β-blocker use and RFS.

Overall, use of β-blockers had no prognostic effect on RFS (HR, 0.96; 95% confidence interval (CI), 0.70 to 1.31). RFS was improved among patients using β-blockers in the pembrolizumab arm (HR 0.67, 95% CI 0.38-1.19) but not in the placebo arm (HR 1.15, 95% CI 0.80-1.66), though this difference was not statistically significant (P = .12).

Among patients who received β-blockers, those in the pembrolizumab arm had a lower likelihood of recurrence (HR, 0.34; 95% CI 0.18 to 0.65), compared to those not using b-blockers (HR, 0.59; 95% CI 0.48 to 0.71), though this was not considered significant.

“This study suggests no prognostic effect of β-blockers in resected high-risk stage III melanoma. However, β-blockers may predict improved efficacy of adjuvant pembrolizumab treatment,” concluded Dr Kennedy and colleagues.

“The combination of immunotherapy with β-blockers merits further investigation,” they added.

Source:

Kennedy O, Kicinski M, Valpione S, et al. Prognostic and predictive value of β-blockers in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma. Eur J Cancer. Published online February 24, 2022. doi:10.1016/j.ejca.2022.01.017.