FGFR-altered metastatic urothelial carcinoma in the real-world setting: Insight from the multicenter, prospective, non-interventional Italian registry of advanced/metastatic urothelial carcinoma (SATURNO)—A FICOG and Meet-URO study.

Abstract

681 Background: The therapeutic landscape of metastatic Urothelial Carcinoma (mUC) is rapidly evolving, alongside increasing opportunities to analyze molecular alteration and molecular classification. FGFR alteration (FGFRa) occur in about 15-20% of mUC patients. Data from randomized-controlled THOR trial demonstrated the clinical efficacy of erdafitinib, an FGFR 1-4inhibitor, in pretreated FGFR3/2a mUC. So, real-world data (RWD) on FGFRa patients remain an unmet need. Methods: SATURNO (NCT06235268) is an Italian, multicenter, prospective, non-interventional study enrolling all mUC patients managed at the participant institutions from Nov 2023 to Sept 2025. The Web National Registry includes patients with metastatic disease or with nodal involvement not suitable to surgery. Participating institutions were selected to adequately represent different geographical area. Results: A total of 237 patients were tested for FGFRa. Among them, 171 (72%) were FGFR3/2a and 66 (28%) were FGFR wild-type (WT). In the FGFR3/2a group, 134/171 (78%) were male and 37/171 (22%) were female; 165/171 (96%) had pure urothelial carcinoma histology. The most common metastatic sites were lung (61/171, 35%), liver (21/171, 12%), bone (41/171, 24%), and retroperitoneal lymph nodes (50/171, 29%). Compared with FGFR WT patients, older age was significantly associated with FGFR3/2a (OR 1.05, 95% CI 1.02–1.09, p = 0.003). Retroperitoneal lymph node involvement was less frequent among FGFR3/2a patients (29% vs 44%, OR 0.53, 95% CI 0.29–0.95, p = 0.033). FGFR3/2a tended to be more common in upper tract urothelial carcinomas (UTUC) compared with bladder tumors (23.4% vs 12.1%, OR 2.12, 95% CI 0.98–5.15, p = 0.073). FGFR3/2a patients were less likely to receive maintenance therapy (OR 0.36, 95% CI 0.19–0.65, p < 0.001). Among patients treated with platinum-based combinations (91/171, 53%), 41/91 (45%) FGFR3a patients received avelumab maintenance compared to 31/58 (53%) in the FGFR WT subgroup. Additionally, 26/91 (29%) FGFR3a patients had primary refractory disease to platinum-based therapy, compared with 14/58 (24%) among FGFR WT patients. Conclusions: RWD from this prospective registry show that FGFR3/2a is more common in older patients and, consistent with previous reports, tends to occur more frequently in UTUC. Retroperitoneal nodal involvement, usually associated with better prognosis, is less common in FGFR3/2a. FGFR3/2a are less likely to receive avelumab maintenance therapy due to primary progression to platinum-based combination. Acknowledgments: The IT infrastructure on which the urothelial tumor registry is based was developed thanks to the unconditional support of Gilead Sciences. Clinical trial information: NCT06235268 .