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

Abstract

BackgroundClinical 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–). ObjectiveTo analyze the outcomes of patients with mUC and any FGFRa (mutations or fusions) who received anti–PD-(L)1 therapy. Design, setting, and participantsIn 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 analysisInvestigator‑determined overall response rate (ORR), disease control rate (DCR), and overall survival (OS) were assessed in multivariate and unadjusted analyses. Results and limitationsNinety-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. ConclusionsSome 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 summaryPatients 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.