Final overall survival of ARIES trial evaluating first line avelumab monotherapy for patients with advanced urothelial cancer (aUC) unfit for cisplatin and outcome analysis based on baseline characteristics.

797 Background: ARIES trial evaluated avelumab monotherapy in PD-L1+ve aUC patients (pts) not eligible to cisplatin-based chemotherapy, reaching its primary endpoint (Iacovelli R et al. ASCO-GU 2022). Treatment landscape for aUC has changed since enfortumab-vedotin and pembrolizumab (EV+P) has become the new standard for platinum-eligible pts reporting also a mPFS of 10.6 mos and 1-y OS rate of about 80% in cisplatin ineligible (carboplatin-eligible) pts. Unfortunately, up to 20% of pts are not eligible to platinum-based chemotherapy (PBC) and guidelines continue to recommend immunotherapy alone. Methods: Pts with PDL1+ve aUC and not eligible for cisplatin-based chemotherapy were enrolled and treated with avelumab until progression of disease. Here we reported the final OS, and we evaluated the baseline differences between pts with longer PFS compared to those who immediately progressed. Baseline characteristic included in this analysis were sites of metastases, performance status, body mass index (BMI), haematological values and the Neutrophils-to-Lymphocytes Ratio (NLR). Results: 71 pts were enrolled, the median age was 75 years (range 38 – 88); bladder cancer was the primary tumour in 73.2% of cases, 25.3% had liver metastases, 31% had ECOG=2 and 31% had renal function <50ml/min. After a median FU of 52 mos, the median OS was 10.3 mos (95%CI 5.3 – 15.3) and the median PFS was 2.1 mos (95%CI 1.8 – 2.4). 26 pts (37%) received subsequent therapies, with gem+carbo as most frequently used (15 pts, 21%). A total of 18 pts (25%) had a PFS ≥9 mos while 44 (62%) had a PFS ≤3 mos. Significant differences between these two groups were the presence of liver mets (11% vs. 36%; p=0.047), the presence of node only disease (39% vs 5%; p<0.001) and the rate of pts with NLR>4 (22% vs. 61%; p=0.005). At multivariable analysis only NLR>4 and liver mets were confirmed to be independent prognostic factors. The 27 pts (38%) without liver mets and with NLR>4 had significantly (p=0.001) prolonged mPFS (7.7 vs. 1.9 mos), mOS (20.4 vs. 5.7 mos), and 1y OS rate (67% vs. 32%). Conclusions: ARIES trial confirmed the activity of avelumab in cisplatin-ineligible aUC pts including those not eligible to PBC. This analysis also identified the absence of liver mets and low values of NRL as potential markers of significant benefit from immunotherapy alone. This evidence can be used for a personalized approach in the evolving treatment landscape of aUC. Clinical trial information: NCT03891238 .