Predictive value of fibroblast growth factor receptor (FGFR) mutations and gene fusions on anti-PD-(L)1 treatment outcomes in patients (pts) with advanced urothelial cancer (UC).

Abstract

419 Background: FGFR alterations have been shown to be associated with immunologically “cold” UC tumors with low immune marker expression and T cell infiltrate, a poorly receptive environment for immune checkpoint inhibitors. Using a real world matched clinical and genomic dataset of pts with advanced UC, we explored their predictive value in pts receiving anti-PD-(L)1 therapy. Methods: The Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB) contained full clinical and treatment information and molecular data on a cohort of pts with confirmed advanced UC. The populations of interest are FGFR+ and FGFR- patients determined by the presence or absence of a prespecified panel of FGFR2/3 mutations and fusions. Overall survival (OS), measured from the start of anti-PD-(L)1 therapy, was analyzed using Kaplan-Meier estimation and Cox proportional hazards models adjusted for left truncation (delayed entry model). Results: 118 pts ( FGFR+ n = 26, FGFR- n = 92) treated with anti-PD-(L)1 therapy for advanced UC were assessed for OS. Median OS for FGFR+ pts who received any line of anti-PD-(L)1 therapy (n = 26) was 3.1 mo vs 6.1 mo for FGFR- pts (n = 92) (hazard ratio [HR] 1.33, 95% CI 0.78-2.26, p = 0.30). For first-line anti-PD-(L)1 therapy, median OS in FGFR+ pts (n = 12) was 4.7 mo vs 11.3 mo for FGFR- pts (n = 28) (HR 1.94, 95% CI: 0.78-4.82, p = 0.15); median OS in second-line were 3.1 mo (n = 12) vs 6.1 mo (n = 47), respectively (HR 1.17, 95% CI 0.53-2.59, p = 0.70). Per multivariate analysis, FGFR+ status appears to be associated with poorer OS in pts treated with any line of anti-PD-(L)1 therapy (HR 1.25, 95% CI 0.71-2.21, p = 0.43). Conclusions: These real-world data suggest that FGFR+ pts following anti-PD-(L)1 therapy for advanced UC may be associated with a trend in poorer overall survival outcome compared with FGFR- pts. These findings are in alignment with treatment history data from BLC2001 (Siefker-Radtke A, et al. ASCO-GU 2018), which showed low response rates to prior anti-PD-(L)1 therapies among FGFR+ pts.