Impact of β-adrenergic blockade on efficacy of immunotherapy in patients with metastatic clear cell renal cell carcinoma.

e16529 Background: Immunotherapy (IO) has become a cornerstone in the standard of care of patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC). Recent studies suggest concomitant beta-blockers (BB) use may improve the effectiveness of IO in melanoma by increasing CD8+ T cells tumor infiltration through β-adrenergic blockade. Herein, we assess the impact of BB on the clinical outcomes of pts with mccRCC treated with IO-based regimens in first-line (1L) settings. Methods: Real-world data from Dana-Farber Cancer Institute and the University of Texas Southwestern Medical Center were collected retrospectively. Pts with mccRCC who received 1L standard of care IO-based regimens, including dual-IO or IO in combination with vascular endothelial growth factor-targeted therapies (IO+VEGF-TT) were included. Pts receiving BB at the 1L initiation were classified as BB-treated pts, while pts who were not on BB at 1L initiation were labeled as BB-untreated pts. Time to treatment failure (TTF) and overall survival (OS) were compared between groups using a multivariable Cox regression adjusting for age at 1L start, body mass index (BMI), and IMDC risk group. Objective response rate (ORR; responders vs. non-responders/not evaluable) per RECIST 1.1 criteria was compared between groups using a Chi-Squared test. Results: Our cohort included 171 pts with mccRCC, 134 (78.4%) were male, and the median (Q1-Q3) age was 62 (56-68) years. A total of 55 deaths were observed. The median follow-up of pts was 28.1 months. At 1L treatment initiation, 52 (30.4%) pts were receiving BB. BB-treated pts (vs. those not) were older (65.1 vs 60.8; p=0.003) and had higher BMI (31.1 vs. 29; p=0.004) at 1L initiation. BB-treated pts (vs. those not) had comparable TTF (adjusted HR (aHR) = 1.0; 95% confidence interval (CI): 0.7-1.5; p=0.88) and comparable OS (aHR=1.1; 95%CI: 0.6-2.0; p=0.67). BB-treated pts (vs. those not) had a numerically increased ORR, but this difference was not statistically significant (31/52, 59.6% vs. 59/119, 49.6%; p=0.29). A sensitivity analysis within each of dual-IO (n=83, 48.5%) and IO+VEGF-TT (n=88, 51.5%) subgroups showed similar results (Table). Conclusions: This is the first effort to investigate the impact of β-adrenergic blockade on IO activity in pts with mccRCC. While previous data suggest concomitant BB use may enhance IO efficacy in pts with melanoma, our results show that the use of BB was not associated with better IO effectiveness in pts with mccRCC. Limitations of the study arise from its retrospective design. Table: see text