%0 Journal Article
%T Outcomes of Patients with Advanced Urothelial Carcinoma after Anti-programmed Death-(ligand) 1 Therapy by Fibroblast Growth Factor Receptor Gene Alteration Status: An Observational Study.
%A Rezazadeh Kalebasty A
%A Benjamin DJ
%A Loriot Y
%A Papantoniou D
%A Siefker-Radtke AO
%A Necchi A
%A Naini V
%A Carcione JC
%A Santiago-Walker A
%A Triantos S
%A Burgess EF
%J Eur Urol Open Sci
%V 47
%N 0
%D Jan 2023
%M 36601039
%F 3
%R 10.1016/j.euros.2022.11.001
%X <B>UNASSIGNED: </B>Clinical outcomes of anti-programmed death‑(ligand) 1 (anti-PD-[L]1) therapy in patients with locally advanced or metastatic urothelial carcinoma (mUC) and fibroblast growth factor receptor alterations (FGFRa+) remain unclear; recent studies have reported either comparable or poorer outcomes versus patients without FGFR alterations (FGFRa-).<BR><B>UNASSIGNED: </B>To analyze the outcomes of patients with mUC and any FGFRa (mutations or fusions) who received anti-PD-(L)1 therapy.<BR><B>UNASSIGNED: </B>In this noninterventional, retrospective, multicenter study, clinical practice data were collected from FGFRa+/- patients who received prior immunotherapy between May 2018 and July 2019.<BR><B>UNASSIGNED: </B>Investigator‑determined overall response rate (ORR), disease control rate (DCR), and overall survival (OS) were assessed in multivariate and unadjusted analyses.<BR><B>UNASSIGNED: </B>Ninety-four patients (66% men; median age, 63 yr) with mUC and known FGFR status were included; 38 (40%) were FGFRa+ and 56 (60%) were FGFRa-. In FGFRa+ versus FGFRa- patients who received any line of anti-PD-(L)1 therapy (n = 92), ORR, DCR, and OS were 16% versus 26%, 29% versus 52% (relative risk: 1.14 [95% confidence interval {CI}, 0.92-1.40]; p = 0.3), and 8.57 versus 13.2 mo (hazard ratio [HR]: 1.33 [95% CI, 0.77-2.30]; p = 0.3), respectively. A multivariate analysis provided some evidence supporting shorter OS in FGFRa+ versus FGFRa- (any line of anti-PD-L[1] therapy; HR: 1.81 [95% CI, 0.99-3.31]; p = 0.054). Limitations include this study's retrospective nature and a potential selection bias from small sample size.<BR><B>UNASSIGNED: </B>Some evidence of lower response rates and shortened OS following anti-PD-(L)1 therapy was observed in FGFRa+ patients. The phase 3 THOR study (NCT03390504) will prospectively compare FGFRa+ patients with advanced mUC treated with erdafitinib versus pembrolizumab.<BR><B>UNASSIGNED: </B>Patients with metastatic urothelial carcinoma and prespecified fibroblast growth factor receptor alterations (FGFRa) potentially have worse clinical outcomes when treated with anti-PD-(L)1 therapy than those without FGFRa.