Fibroblast Growth Factor Receptor Status and Advanced Bladder Cancer Progression: a Retrospective Study

Background: FGFR alterations (FGFRalt) appear enriched in approximately 15% of cases of mUC. Small sample sizes have limited data on whether FGFRalt in mUC have a prognostic impact or predictive benefit for particular treatments. The objective of this study was to evaluate the association between tumor FGFRalt and clinical outcomes of patients with advanced UC or mUC regardless of therapy type and status. Methods: A convenience sample of oncologists and urologists across the United States provided patient-level data on 400 patients with stage IIIb or IV UC via a standardized questionnaire over a 1-month period (August 17, 2020 – September 20, 2020). Th study design enriched for FGFRalt by requiring physicians to provide at least one FGFRalt patient record. The questionnaire included physician characteristics, patient demographic information, FGFR status, therapy given, response, and clinical and radiographic measures of progression. Patient records were eligible for inclusion if they were identified and treated between July 1, 2017 and June 30, 2019. Cox proportional hazards models were used to estimate adjusted risk of disease progression by FGFR status. Results: A total of 104 physicians (58.7% medical oncologists, 31.7% hematologic oncologists, and 9.6% urologic oncologists) contributed 414 patient records Overall, 73.9% of the patients were male and the average age was 64.5 years (SD 10.6). Median follow-up was 15 months. Of the 414 patients, 218 (52.7%) had FGFRalt and 196 (47.3%) had FGFR wild-type (FGFRwt) mUC. Of the 218 patients with FGFRalt, 47.2% were treated with front-line chemo, 27.5% with a programmed death-ligand 1 inhibitor (PD-L1), 11.5% with chemo + PD-L1, and 13.8% with other treatments. Of the 196 FGFRwt patients , 63.2% were treated with front-line chemo, 21.9% with PD-L1, 12.2% with chemo + PD-L1, and 2.6% with other treatments. There was no difference in response or progression status for those receiving front-line chemo (HR, 1.15; 95% CI, 0.86-1.55). Among 97 patients (55 FGFRalt and 42 FGFRwt) who received PD-L1 alone as front-line therapy, FGFRalt patients had an adjusted risk of progression 2 times higher than their FGFRwt counterparts (HR, 2.12; 95% CI, 1.13-4.00). Conclusions: Patients with FGFRalt mUC progressed earlier than FGFRwt patients treated with front-line PDL-1 inhibitors; however, there was no difference in progression for patients treated with chemotherapy based upon FGFR status. This real-world study used a survey design to efficiently generate a relatively large FGFRalt dataset, mitigating a core limitation of other studies assessing the patient population with FGFRalt. Further work is warranted to validate these results and determine the optimal strategy for treating the patient with FGFRalt mUC. Gene expression profiling of FGFRalt mUC samples from clinical trials will help determine the potential impact of subtype or other features that may benefit from therapy