Treatment options and outcome of patients with metastatic renal cell carcinoma with brain or bone metastases: Real world evidence from a German retrospective multi-center analysis.

Abstract

387 Background: Brain (BM) and bone metastases (BOM) in renal cell carcinoma (RCC) are associated with poor outcome. We evaluated real-world treatment paradigms of RCC patients with BM and BOM. Methods: We retrospectively analyzed RCC patients with BM and/or BOM treated at 18 German tertiary cancer centres from 2003 to 2023. Adverse events (AE) were reported according to CTCAE 5.0, objective response rate (ORR) according to local standard. Overall survival (OS) was calculated from start of treatment to progression or death, respectively and determined by KM plots. Results: We included 453 patients with a median age of 64 years (IQR 56-71). 93% of all patients had BOM, 15% BM and 8% both. Most patients (79%) had clear cell RCC, 7% of all patients had sarcomatoid differentiation. 82% of patients had an ECOG PS of 0/1. IMDC risk was favorable/intermediate/poor in 20/56/24%. 64% received prior nephrectomy. Patients with BOM received first-line IO-combinations in 61% (IO-IO: 38%, TKI-IO: 62%), TKI-monotherapy in 39%, while patients with BM received IO-combinations in 68% (IO-IO: 37%, TKI-IO: 63%) and TKI in 32%. IO-based first-line therapy increased from 2003 to 2023. AE of all grades occurred in 87% and 69% during IO-based therapy or TKI monotherapy, and CTCAE grade ≥ 3 in 42% or 25%. Best ORR and survival outcomes with median follow-up of 23 months (IQR 9-42) are described in table 1. 56% and 58% of all patients with BOM and BM received second-line treatment, with Cabozantinib (34%; 34%) and Nivolumab (17%, 23%) being the most common treatment options. In the subgroup of RCC with sarcomatoid features (n=36), 34 patients had BOM and 7 had BM, of which were treated with IO-combinations in 88% (BOM; IO-IO: 41%, TKI-IO: 59%) or 66% (BM; IO-IO: 50%, TKI-IO: 50%) and TKI-monotherapy in 12% (BOM) or 34% (BM) of all patients. Response rates (ORR/SD/PD) were 48%/28%/24% for IO-based therapy and 0%/50%/50% for TKI-monotherapy in RCC with sarcomatoid features, mOS was 41 months (95% CI 16.7-65.3). Conclusions: RCC patients with BOM and BM are increasingly treated with IO-combinations but lead to higher rates of AE grade ≥ 3. In patients with BOM, IO-TKI revealed higher ORR compared to IO-IO combination, but not in patients with BM. However, the small sample size and retrospective design are major limitations of our analysis. Prospective studies evaluating treatment options for BOM and BM in patients with RCC is critical. [Table: see text]