Abstract INTRO Programmed cell death protein 1 (PD1)-inhibitor, nivolumab, and cytotoxic T-lymphocyte-associated protein 4 (CTLA4)-inhibitor, ipilimumab, have been shown to be efficacious in treatment of metastatic renal cell carcinoma (RCC). Clinical trials utilizing PD1- and CTLA4-inhibitors to treat RCC have demonstrated an increase in survival, however history of brain metastases (BM) has typically excluded patients from these trials. This study evaluated the benefit of these agents in terms of overall survival from RCC diagnosis (OSRCC), from BM diagnosis (OSBM) and frequency of BM occurrence in patients with metastatic RCC. METHODS A retrospective single-center review between 2011–2018 identified 1149 patients treated for RCC. The study group included patients who received immunotherapy and/or non-immunotherapeutic agents during the course of their disease. Data analyzed included demographic information, systemic treatments, OS and status of BM. Two-sided Fisher’s exact test was used to evaluate frequency of BM occurrence. OSRCC and OSBM were assessed using Kaplan-Meier curves and log-rank tests. RESULTS Of 1149 patients, 425 (35.6%) were treated with systemic therapies during their clinical course and divided into two treatment groups: those receiving immunotherapy (n=125) and those receiving non-immunotherapeutic agents (n=300). OSRCC was improved in the immunotherapy group (80.3months 95%CI 58.7–101.9 vs 45.0 95%CI 36.4–53.6, p=0.003), with 1-, 3- and 5-year survival of 93.6%, 74.2% and 62.6%. BM were diagnosed in 113 of 425 patients. Use of immunotherapy was associated with increased OSBM (21.7months vs 8.5, p=0.001). In patients receiving systemic treatment prior to a potential BM diagnosis, BM occurred at a frequency of 8.0% in the immunotherapy group compared to 17.7% for the control (n=100 and n=266 respectively, p=0.021). CONCLUSION Immunotherapy not only improves OSRCC and OSBM, but also decreases the incidence of BM in patients with metastatic RCC. Prospective clinical trials are needed to further evaluate the activity of immunotherapy in treatment of RCC BM.
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