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

Background: 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–). Objective: To analyze the outcomes of patients with mUC and any FGFRa (mutations or fusions) who received anti–PD-(L)1 therapy. Design, setting, and participants: In this noninterventional, retrospective, multicenter study, clinical practice data were collected from FGFRa+/– patients who received prior immunotherapy between May 2018 and July 2019. Outcome measurements and statistical analysis: Investigator‑determined overall response rate (ORR), disease control rate (DCR), and overall survival (OS) were assessed in multivariate and unadjusted analyses. Results and limitations: 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. Conclusions: 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. Patient summary: 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.