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Fibroblast growth factor receptor: A systematic review and meta-analysis of prognostic value and therapeutic options in patients with urothelial bladder carcinoma

M. Kardoust Parizi, V. Margulis, Y. Lotan, K. Mori, SF. Shariat

. 2021 ; 39 (7) : 409-421. [pub] 20210226

Language English Country United States

Document type Journal Article, Meta-Analysis, Systematic Review

To evaluate the oncologic prognostic value of fibroblast growth factor receptor (FGFR) and to assess the safety and efficacy of its inhibitors in patients with urothelial bladder carcinoma. A literature search using PubMed, Scopus, and Cochrane Library was conducted on June 2020 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The pooled recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS) were calculated using a fixed or random effects model in patients with nonmuscle invasive bladder cancer (NMIBC). Overall, 62 studies comprising 9,229 patients were eligible and included in this systematic review and meta-analysis. Both FGFR3 mutation and protein overexpression were significantly associated with RFS, PFS, CSS, and overall survival. FGFR3 mutation was associated with worse RFS and better PFS (pooled hazard ratio: 1.30; 95% confidence interval: 1.08-1.57, and pooled hazard ratio: 0.62; 95% confidence interval: 0.42-0.92, respectively) in patients with NMIBC. In 11 studies reporting on the response to FGFR inhibitors, complete response rates, disease control rates, and overall response rate of 0% to 8%, 59.3% to 64.2%, and 40% were reported for dovitinib, infigratinib, and erdafitinib, respectively. Based on this study, FGFR3 mutation is a statistically significant prognostic factor for RFS in NMIBC. FGFR inhibitors have measurable benefit in patients with advanced and metastatic urothelial carcinoma. However, the results of ongoing RCTs and future well-designed studies are awaited to capture the differential biologic and clinical behavior of tumors harboring FGFR while helping to identify those who are most likely to benefit from FGFR inhibitors.

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$a Kardoust Parizi, Mehdi $u Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
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$a Fibroblast growth factor receptor: A systematic review and meta-analysis of prognostic value and therapeutic options in patients with urothelial bladder carcinoma / $c M. Kardoust Parizi, V. Margulis, Y. Lotan, K. Mori, SF. Shariat
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$a To evaluate the oncologic prognostic value of fibroblast growth factor receptor (FGFR) and to assess the safety and efficacy of its inhibitors in patients with urothelial bladder carcinoma. A literature search using PubMed, Scopus, and Cochrane Library was conducted on June 2020 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The pooled recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS) were calculated using a fixed or random effects model in patients with nonmuscle invasive bladder cancer (NMIBC). Overall, 62 studies comprising 9,229 patients were eligible and included in this systematic review and meta-analysis. Both FGFR3 mutation and protein overexpression were significantly associated with RFS, PFS, CSS, and overall survival. FGFR3 mutation was associated with worse RFS and better PFS (pooled hazard ratio: 1.30; 95% confidence interval: 1.08-1.57, and pooled hazard ratio: 0.62; 95% confidence interval: 0.42-0.92, respectively) in patients with NMIBC. In 11 studies reporting on the response to FGFR inhibitors, complete response rates, disease control rates, and overall response rate of 0% to 8%, 59.3% to 64.2%, and 40% were reported for dovitinib, infigratinib, and erdafitinib, respectively. Based on this study, FGFR3 mutation is a statistically significant prognostic factor for RFS in NMIBC. FGFR inhibitors have measurable benefit in patients with advanced and metastatic urothelial carcinoma. However, the results of ongoing RCTs and future well-designed studies are awaited to capture the differential biologic and clinical behavior of tumors harboring FGFR while helping to identify those who are most likely to benefit from FGFR inhibitors.
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$a Margulis, Vitaly $u Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX
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$a Mori, Keiichiro $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
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$a Shariat, Shahrokh F $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, Second Faculty of Medicine, Charles University, Prag, Czech Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan; European Association of Urology research foundation, Arnhem, The Netherlands. Electronic address: sfshariat@gmail.com
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