Effect of concurrent beta-blocker (BB) use in patients receiving immune checkpoint inhibitors for metastatic urothelial (mUC) and renal cell carcinomas (mRCC).
467 Background: Stress-induced adrenergic signaling suppresses the immune system. A pre-clinical mouse model has shown that pharmacologic beta-blockade can stimulate CD8+ T-cell activity, and as a result improve efficacy of checkpoint inhibitors (CPI) to inhibit growth in solid tumors. Herein, we investigate the effect of BB on outcomes of patients receiving immunotherapy in mUC and mRCC. Methods: Using the Mount Sinai Genitourinary (GU) Cancer Biorepository, an IRB approved database containing all consented GU cancer patients seen between 2010-2018, we identified patients with either UC or RCC that have received CTLA-4 and/or PD-1/PD-L1 blockade. Patients who received only 1 dose of CPI were excluded from this analysis. A descriptive analysis was performed to assess clinical characteristics and treatment response. Overall Survival (OS) was calculated with Kaplan-Meier curves and cox proportional hazard models. Results: We identified 34 evaluable patients with mUC and 14 with mRCC that received CPI (Table). The median age at initiation was 69 years (39–91 years) and 81.2% (39/48) received prior chemotherapy and/or molecular targeted therapies. The mean duration of therapy was longer in the BB group compared to non-BB group (10.6 vs. 4.0 mo). For patients with mUC, the overall response rate (ORR) was 62.5% vs. 12.5% in favor of the BB group. For the patients with mRCC, the ORR was 40.0% vs. 10.0% in favor of the BB group. There were more outstanding responders (>1 year) in the BB group when compared with the non-BB group (41.2% vs. 6.5%). Patients with BB use had significantly improved median OS (NR vs. 11.6 mo, p = 0.004) when compared to those who did not receive BB. Conclusions: In this single-center cohort, the concurrent use of BB receiving CPI therapy is associated with an improved ORR, duration of therapy, and OS. Although this is hypothesis generating, the addition of BB is a promising strategy to improve response of immunotherapy, and prospective validation of this approach will be needed. [Table: see text]