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: Investigator­determined 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.

Prognostic and Predictive Value of Fibroblast Growth Factor Receptor Alterations in High-grade Non-muscle-invasive Bladder Cancer Treated with and Without Bacillus Calmette-Guérin Immunotherapy.

BACKGROUND: Limited data are available on the prognostic and predictive value of fibroblast growth factor receptor alterations (FGFRa) relative to clinical outcomes in patients with non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To determine whether FGFRa may be clinically useful in stratifying for treatment response in a real-world cohort of patients with pT1 NMIBC treated and untreated with bacillus Calmette-Guérin (BCG) instillation therapy. DESIGN, SETTING, AND PARTICIPANTS: A pooled dataset of matched clinical and genomic data (1992-2015) for pT1 NMIBC patients was assessed by the Bladder Cancer Research Initiative for Drug Targets in Germany consortium. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Key efficacy outcomes were recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS), which were estimated by Kaplan-Meier analysis, with hazard ratios calculated using a multivariate Cox proportional-hazard model. RESULTS AND LIMITATIONS: In this retrospective study of 263 patients with high-grade NMIBC, at a median follow-up of 63 mo, 32% showed recurrence and 15% progressed to muscle-invasive bladder cancer. FGFRa were found in 43% of patients, including 39% mutations and 5.7% fusions. FGFRa were associated with lower rates of concomitant carcinoma in situ. Among patients with or without FGFRa, there was no significant difference in PFS, RFS, and DSS in those who were BCG treated or BCG naive, or in the overall population. Limitations include the retrospective design from a single-center setting. CONCLUSIONS: In patients with high-risk NMIBC, FGFRa were frequently observed. Patients with FGFRa who often exhibit recurrence/relapse after BCG treatment have a high unmet need. PATIENT SUMMARY: Our retrospective study suggests that fibroblast growth factor receptor alterations (FGFRa) occur frequently in non-muscle-invasive bladder cancer (NMIBC). Outcomes were similar with or without FGFRa in patients with NMIBC, both overall and for standard bacillus Calmette-Guérin (BCG) treatment.