Efficacy and safety of first- versus second-generation fibroblast growth factor receptor (FGFR) inhibitors in advanced or metastatic urothelial carcinoma with FGFR alterations: a systematic review and meta-analysis
- 1Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute , ,
Abstract
Introduction: We reviewed the clinical studies on fibroblast growth factor receptor (FGFR) inhibitors for the treatment of urothelial carcinoma to conduct the meta-analysis of clinical efficacy and safety, aiming to provide more precise treatment options for patients with FGFR alterations.
Method: We performed the literature search and screening, then calculated and analyzed using the STATA 14.0 software and Review Manager 5.3 software.
Results: A total of 1528 patients from seventeen studies focusing on seven different FGFR inhibitors were collected. The efficacy analysis indicated the pooled objective response rate (ORR) was 32% (95% CI 26% to 39%) and the pooled disease control rate (DCR) was 64% (95% CI 53% to 75%) for patients with FGFR alterations treated with FGFR inhibitors. The pooled ORR and DCR of second-generation FGFR inhibitors were both significantly higher than those of first-generation FGFR inhibitors (ORR: 0.35, 95% CI 0.29 to 0.41 versus 0.07, 95% CI 0.02 to 0.16, p < 0.001; DCR: 0.68, 95% CI 0.61 to 0.75 versus 0.27, 95% CI 0.16 to 0.40, p < 0.001). The safety analysis indicated any-grade TRAEs were comparable between first- and second-generation FGFR inhibitors, but grade ≥3 TRAEs were significantly less frequent with second-generation FGFR inhibitors versus first-generation FGFR inhibitors (0.49, 95% CI 0.40 to 0.57 versus 0.67, 95% CI 0.57 to 0.76; p = 0.006). The common target toxicities associated with FGFR inhibitors, such as hyperphosphatemia, stomatitis and PPES, were more frequently occurred in second-generation FGFR inhibitors compared to first-generation FGFR inhibitors.
Conclusion: The second-generation FGFR inhibitors have advantages in both efficacy and safety, but special adverse reactions still require additional attention.
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BibTeX
@article{wang2026efficacy,
title = {{Efficacy and safety of first- versus second-generation fibroblast growth factor receptor (FGFR) inhibitors in advanced or metastatic urothelial carcinoma with FGFR alterations: a systematic review and meta-analysis}},
author = {Zhe Wang and Bo Shao and Danxue Huang and Liyuan Ke},
journal = {Frontiers in pharmacology},
year = {2026},
month = sep,
doi = {10.3389/fphar.2026.1850131},
url = {https://europepmc.org/article/PMC/PMC13662917},
note = {CC BY},
}
RIS
TY - JOUR
TI - Efficacy and safety of first- versus second-generation fibroblast growth factor receptor (FGFR) inhibitors in advanced or metastatic urothelial carcinoma with FGFR alterations: a systematic review and meta-analysis
AU - Zhe Wang
AU - Bo Shao
AU - Danxue Huang
AU - Liyuan Ke
PY - 2026
DA - 2026/09/30
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1850131
UR - https://europepmc.org/article/PMC/PMC13662917
AB - Introduction: We reviewed the clinical studies on fibroblast growth factor receptor (FGFR) inhibitors for the treatment of urothelial carcinoma to conduct the meta-analysis of clinical efficacy and safety, aiming to provide more precise treatment options for patients with FGFR alterations. Method: We performed the literature search and screening, then calculated and analyzed using the STATA 14.0 software and Review Manager 5.3 software. Results: A total of 1528 patients from seventeen studies focusing on seven different FGFR inhibitors were collected. The efficacy analysis indicated the pooled objective response rate (ORR) was 32% (95% CI 26% to 39%) and the pooled disease control rate (DCR) was 64% (95% CI 53% to 75%) for patients with FGFR alterations treated with FGFR inhibitors. The pooled ORR and DCR of second-generation FGFR inhibitors were both significantly higher than those of first-generation FGFR inhibitors (ORR: 0.35, 95% CI 0.29 to 0.41 versus 0.07, 95% CI 0.02 to 0.16, p < 0.001; DCR: 0.68, 95% CI 0.61 to 0.75 versus 0.27, 95% CI 0.16 to 0.40, p < 0.001). The safety analysis indicated any-grade TRAEs were comparable between first- and second-generation FGFR inhibitors, but grade ≥3 TRAEs were significantly less frequent with second-generation FGFR inhibitors versus first-generation FGFR inhibitors (0.49, 95% CI 0.40 to 0.57 versus 0.67, 95% CI 0.57 to 0.76; p = 0.006). The common target toxicities associated with FGFR inhibitors, such as hyperphosphatemia, stomatitis and PPES, were more frequently occurred in second-generation FGFR inhibitors compared to first-generation FGFR inhibitors. Conclusion: The second-generation FGFR inhibitors have advantages in both efficacy and safety, but special adverse reactions still require additional attention.
SN - 1663-9812
ER -