Safety and efficacy of FGFR inhibitors in urothelial carcinoma: A systematic review and meta-analysis.

Abstract

782 Background: Urothelial carcinoma is the most frequently occurring bladder cancer and originates from urothelial cells lining the bladder and the urinary tract. Fibroblast growth factor receptor (FGFR) inhibitors are the emerging treatment option, due to their ability to alter FGFR signaling which plays a role in tumor proliferation, survival, and angiogenesis. This study aims to assess the efficacy of FGFR inhibitors for urothelial carcinoma. Methods: We conducted a systematic review and single-arm meta-analysis by systematically searching PubMed, Cochrane, and Embase for studies evaluating the efficacy and/or safety of FGFR inhibitors for urothelial carcinoma. The primary measures of effect were hazard ratios (HRs) and the proportion of events per 100 observations, both with 95% confidence intervals (CIs), pooled using a random-effects model with a generalized linear mixed model (GLMM). Heterogeneity was assessed using the I² statistic and Cochran’s Q test. Statistical analyses were performed using RStudio v4.3.3. Results: We included 19 studies, comprising two cohort studies and 17 clinical trials, five of which were randomized controlled trials (RCTs), with a combined total of 1,187 patients. The pooled median overall survival (mOS) was 8.77 months (95% CI, 7.28; 10.56), the pooled median progression-free survival (mPFS) was 3.46 months (95% CI, 2.73; 4.40), and the median duration of response (mDOR) was 5.38 months (95% CI, 4.72; 6.14). The grade ≥ 3 adverse effects rate was 49.43% (95% CI, 35.44; 63.51%). The overall objective response rate (ORR) was 24.16% (95% CI, 17.65; 32.14%), in the subgroup analysis of 218 patients using Erdafitinib ORR was 42.25%. The progressive disease and stable disease rates were 48.64% (95% CI, 38.88; 58.50%) and 26.07% (95% CI, 20.01; 33.21%), respectively. Conclusions: Our meta-analysis suggests that FGFR-targeted treatment regimens show promising clinical activity in urothelial carcinoma with a comparable safety profile to conventional treatment modalities.