Impact of FGFR3 Alterations on First-Line Platinum Based Chemotherapy in Patients With Metastatic or Locally Advanced...

FGFR3 alterations are observed in 10% to 15% of patients with advanced urothelial carcinoma (UC). We aimed to clarify the prognostic and predictive value of FGFR3 alterations in patients receiving first-line platinum-based chemotherapy (PBC) for advanced urothelial carcinoma.

We conducted a multicenter retrospective cohort study including patients with histologically confirmed UC treated in first line with PBC, with or without immune-checkpoint inhibitors (ICIs) administered 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 ICIs, stratified by FGFR3 status.

Between 2016 and 2022, 191 pts were included, of whom 58 (30.4%) had FGFR3-altered tumors (FGFR3^alt). Baseline characteristics were well balanced. ICIs were administered to 34% of patients. After a median follow-up of 32 months, median PFS under PBC was 6.6 months in FGFR3^alt and 7.5 in FGFR3 wild type subgroups (HR = 1.27; P = .15) respectively. Median OS was 22.1 versus 20.8 months (HR = 0.91; P = .658), and ORR in 133 pts were similar across subgroups (70.7% vs. 69.2% respectively). In multivariate analysis, FGFR3 status was not associated with survival.

FGFR3 status did not significantly impact response to PBC in first-line treatment or ICIs. 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.