Real-world management strategies and outcomes of brain metastases in patients with mRCC.

e16531 Background: Brain metastases (BM) occur in 10–20% of patients (pt) with metastatic renal cell carcinoma (mRCC) and are associated with poor prognosis. While local therapies remain standard, real-world outcomes with systemic therapy (ST) are poorly defined. We evaluated outcomes of pt with mRCC and BM according to timing of BM development, local therapy, and ST received. Methods: We conducted a retrospective cohort study using the Canadian Kidney Cancer Information System (CKCis) to identify pt with mRCC and BM diagnosed between January 2011 and September 2025. Patients were categorized as having BM prior to ST initiation (denovoBM) or after ST initiation. Baseline characteristics, treatments, and outcomes were analyzed. Overall survival (OS) was defined as time from ST initiation to death, and progression-free survival (PFS) as time from ST initiation to disease progression or death. Results: A total of 637 pt with mRCC and BM were identified (8.7%); the majority were male (74%, n=471) and had IMDC intermediate and poor risk disease (87.5%, n=464). 21% underwent BM surgery and 92% received radiation therapy. Median follow-up was 28.4 months. Overall, 255 (40%) had denovoBM, while 382 (60%) developed BM after ST initiation. De novo BM: Among pt treated with ipilimumab/nivolumab (I/N), 49.2% experienced disease progression, with 35.4% (n=23) receiving second line ST (2LST). Of those treated with immune checkpoint inhibitor plus tyrosine kinase inhibitor (IO/TKI), 50% experienced progression, with 41.3% (19) receiving 2LST. Among single agent TKI recipients, 89.6% experienced progression, with 54.2% (n=78) of them subsequently receiving 2LST. BM developing after ST initiation: In pt receiving I/N, 43.0% experienced brain progression, with 64.5% receiving 2LST, and for IO/TKI, 83.3% experienced disease progression with 55.6% (N=20) receiving 2LST. Of those receiving single agent TKI, 94.9% experienced progression, with 69.2% (n175=) receiving 2LST. Survival outcomes are shown in table 1. Conclusions: Patients with mRCC and BM have poor outcomes despite contemporary ST, highlighting the unmet need for more effective CNS-active therapies and consideration of baseline brain imaging in higher-risk pt. Survival outcomes by timing of BM relative to ST initiation. Outcome De novo BM BM after ST HR (95% CI) p value Ipilimumab/nivolumab PFS, median (95% CI) 5.49 (4.11–8.18) 4.99 (3.19–11.34) 1.20 (0.84-1.72) 0.32 OS, median (95% CI) 38.60 (30.00–48.89) 34.86 (18.60–59.76) 0.89 (0.58–1.36) 0.58 IO/TKI PFS, median (95% CI) 9.23 (2.66-16.26) 9.69 (5.42–17.25) 1.26 (0.76–2.09) 0.36 OS, median (95% CI) 26.71 (15.90–47.47) 33.05 (20.27–NR) 1.36 (0.74–2.49) 0.32 Single-agent TKI PFS, median (95% CI) 19.15 (15.57–22.31 10.81 (8.18 15.80) 0.88 (0.71–1.10) 0.26 OS, median (95% CI) 35.98 (29.27–40.84) 27.01 (21.88–34.86) 1.09 (0.86–1.38) 0.47