Effect of concurrent beta-blocker use in patients receiving immune checkpoint inhibitors for advanced solid tumors

George Mellgard, Vaibhav G. Patel, Xiaobo Zhong, Himanshu Joshi, Qian Qin, Bo Wang, Anish Parikh, Tomi Jun, Parissa Alerasool, Philip Garcia, Mahalya Gogerly-Moragoda, Amanda Leiter, Emily J. Gallagher, William K. Oh, Matthew D. Galsky, Che Kai Tsao

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose: Stress-induced adrenergic signaling can suppress the immune system. In animal models, pharmacological beta-blockade stimulates CD8 + T-cell activity and improves clinical activity of immune checkpoint blockade (ICB) in inhibiting tumor growth. Herein, we investigated the effect of BB on clinical outcomes of patients receiving ICB in advanced solid tumors. Methods: We retrospectively evaluated patients with solid tumors treated with ICB at our institution from January 1, 2011 to April 28, 2017. The primary clinical outcome was disease control. Secondary clinical outcomes were overall survival (OS), and duration of therapy (DoT). The primary predictor was use of BB. Association between disease control status and BB use was assessed in univariable and multivariable logistic regression. OS was calculated using hazard ratios of BB-recipient patients vs. BB non-recipient patients via Cox proportional hazards regression models. All tests were two-sided at a significance level of 0.05. Results: Of 339 identified patients receiving ICB, 109 (32%) also received BB. In covariate-adjusted analysis, odds of disease control were significantly higher among BB recipients compared to BB-non-recipients (2.79; [1.54–5.03]; P = 0.001). While we did not observe significant association of OS with the use of BB overall, significant association with better OS was observed for the urothelial carcinoma cohort (HR: 0.24; [0.09, 0.62]; P = 0.0031). Conclusions: Concurrent use of BB may enhance the clinical activity of ICB and influence overall survival, particularly in patients with urothelial carcinoma. Our findings warrant further investigation to understand the interaction of beta adrenergic signaling and antitumor immune activity and explore a combination strategy.

Original languageEnglish (US)
JournalJournal of Cancer Research and Clinical Oncology
DOIs
StateAccepted/In press - 2022
Externally publishedYes

Keywords

  • Adrenergic beta-antagonists
  • Immunotherapy
  • Neoplasm

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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