#2721 A safety and survival analysis of sequential systemic anticancer treatment in patients with end-stage kidney disease and metastatic renal cell carcinoma

Abstract Background and Aims Systemic anticancer treatment (SACT) prolongs overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) but is associated with various adverse events (AEs). Many mRCC patients develop chronic kidney disease, that can progress to end-stage kidney disease (ESKD), requiring chronic hemodialysis (HD). Unfortunately, pivotal randomized trials usually exclude cancer patients with ESKD, resulting in a lack of high-quality data on the efficacy and safety of SACT in this population. The incidence of serious AEs, particularly bleeding and infection, and the primary outcome in terms of OS in mRCC patients with ESKD receiving SACT, remains unclear. Method We retrospectively identified all patients with mRCC and ESKD who received SACT with VEGFR inhibitors, immune check point inhibitors (ICI), or mTOR inhibitors, alone or in combinations, at the Institute of Oncology Ljubljana in Slovenia between December 2009 and January 2025. Data on the frequency and severity of bleeding and infections were collected from electronic health records. OS was defined as the duration of time from the initiation of SACT to death. Mean and median OS were calculated across all risk groups according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Results We identified 38 patients with mRCC and ESKD treated with SACT. Their median age at SACT initiation of was 70.5 (64.3–75) years, with 30 patients (79%) being men. According to IMDC criteria, 12 patients had a good prognosis, while 26 (68.4%) had intermediate or poor prognosis. Eighteen patients (47%) experienced a least one cycle of ICI. Before SACT, 25 patients (65.8%) were already on HD and 16 patients (34.2%) later developed ESKD. Three patients (7.9%) had an eGFR of ≤15 ml/min/1.73 m2, and six (15.8%) had an eGFR of 15–29 ml/min/1.73 m2 at SACT start. Eight patients (21%) experienced bleeding episodes before SACT initiation, including three with gastrointestinal bleeding (GIB). Grade 4 epistaxis occurred in three patients, with one patient who developed hemorrhagic shock during first-line treatment with sunitinib. Two patients experienced grade 4 anal hemorrhage, one related to hemorrhoids during sunitinib therapy. Two patients required urgent nephrectomy during pazopanib or sunitinib treatment. One patient required urgent local treatment for massive upper GIB during corticosteroids therapy due to immune-related AEs. Overall, seven patients (18.4%) experienced grade 4 GIB during or after SACT. The cumulative incidence of grade 3/4 bleeding was 0.53 (20 events/38 patients), and all-grade bleeding was 1.24 (47 events/38 patients). Twenty eight patients (73.7%) experienced grade 4 infections during SACT, with seven developing sepsis, and one, experiencing septic shock while on HD and receiving first-line treatment with sunitinib. Across all prognostic groups, the median OS was 32 months (95% CI: 15.7–48.3) and the mean OS was 38 months (95% CI: 25.8–51). All censored patients were alive at the end of the study. Conclusion Serious bleeding and infections are common complications in mRCC and ESKD patients treated with sequential SACT. Clinicians should consider these potentially life-threatening complications when selecting the type and duration of SACT. Given the significant management challenges, treatment should occur in dedicated onco-nephrology services. The IMDC risk model and the primary outcomes for mRCC and ESKD patients warrant further evaluation in prospective trials to enhance treatment strategies and improve outcomes.