Predictive value of fibroblast growth factor receptor (FGFR) alterations on anti-PD-(L)1 treatment outcomes in patients (Pts) with advanced urothelial cancer (UC): Pooled analysis of real-world data.

Abstract

493 Background: The tumor microenvironment in UC harboring FGFR gene alterations is characterized by decreased T-cell infiltration and low immune marker expression, potentially implicating suboptimal response to immune checkpoint inhibitors. The association between FGFR gene mutations/fusions and anti-PD-(L)1 treatment outcomes in advanced UC was assessed using real-world pt data. Methods: A pooled dataset of matched clinical and genomic data for advanced UC pts treated with anti-PD-(L)1 in any line from the Bladder Cancer Research Initiative for Drug Targets in Germany (BRIDGE) Consortium and UNC-CH was assessed. FGFR status was defined by a prespecified panel of FGFR2/3 mutations and fusions. Overall survival (OS) was analyzed using Kaplan-Meier estimates and Cox proportional hazards models. Multivariate analyses were performed using potential prognostic covariates (sex, age, baseline tumor stage, urothelial histology, smoking history, primary tumor location, and ECOG) in a Cox regression model for OS to assess their impact on the effect of FGFR alterations. Results: Median OS for FGFR+ pts (n=28) who received any line of anti-PD-(L)1 therapy was 9.5 mo vs 7.5 mo for FGFR− pts (n=139) (HR: 1.03, 95% CI: 0.60-1.76, p=0.93). Median OS for pts treated with first-line anti-PD-(L)1 was 5.42 mo in FGFR+ pts (n=10) and was not reached for FGFR− pts (n=31) (HR: 2.06, 95% CI: 0.68-6.24, p=0.19); median OS in second-line anti-PD-(L)1 was 6.5 mo (FGFR+; n=14) vs 5.7 mo (FGFR−; n=86) (HR: 0.89, 95% CI: 0.44-1.81, p=0.74). The multivariate analyses showed a significant trend of poorer OS in FGFR+ pts with first-line anti-PD-(L)1 (HR: 10.42, 95% CI: 1.45-74.97, p=0.02); wide CI may be attributed to small sample size for some categories in several covariates. Conclusions: Treatment with first-line anti-PD-(L)1 in FGFR+ pts may be associated with poorer OS outcomes in FGFR+ pts; however, this trend was not observed in FGFR+ pts treated with any line and second-line anti-PD-(L)1. Investigation of the predictive value of FGFR alterations to immunotherapy outcomes in larger real-world pt datasets is warranted.