Impact of FGFR3 alterations on first-line platinum based chemotherapy in patients with metastatic or locally advanced urothelial carcinoma: The retrospective IFUCA study.

Abstract

735 Background: FGFR3 alterations are observed in 10–15% of patients with advanced urothelial carcinoma (UC). While targeted therapies are emerging, the prognostic and predictive value of FGFR3 alterations in the context of first-line platinum-based chemotherapy (PBC) remains unclear. Methods: We conducted a multicenter retrospective cohort study including patients (pts) with histologically confirmed UC treated in first line with PBC (carboplatin or cisplatin), with or without immune checkpoint inhibitor (ICI) as maintenance or second line. Only patients with known FGFR3 status on baseline tumor tissue, locally assessed were included. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), objective response rates (ORR), and PFS with ICI, stratified by FGFR3 status. Results: Between 2016 and 2022, 191 pts were included, of whom 58 (30.4%) had FGFR3-altered tumors (FGFR3^alt). Baseline characteristics were well balanced, although FGFR3^alt patients had more de novo metastatic disease and fewer prior local treatments (HR = 0.65; p = 0.01). After a median follow-up of 32 months, median PFS with PBC was 6.6 months in both FGFR3^alt and wild-type groups (HR = 1.27; p = 0.15) respectively. Median OS was 22.1 vs. 20.8 months (HR = 0.91; p = 0.658), and ORR in 133 pts were similar across subgroups (70.7% vs. 69.2% respectively). ICI was administered to 65 (34%) of patients and no difference in PFS was observed between groups with 4.4 vs 2.9 months (HR = 0.86 ; p = 0.5868) respectively. In multivariate analysis, FGFR3 status was not associated with survival. Conclusions: FGFR3 status did not significantly impact response to PBC in first-line treatment or ICI. These findings underscore that the presence of an FGFR3 alteration does not guide the choice of platinum-based treatment, and the need for prospective biomarker-driven trials to identify best treatment sequences in advanced UC.