Effect of FGFR alteration on prognosis in 1963 urothelial carcinoma patients with immune checkpoint inhibitors: Implying combination of FGFR inhibitor and immunotherapy for FGFR-altered urothelial carcinoma

Immune checkpoint inhibitors (ICIs) are essential for urothelial carcinoma (UC) treatment. Fibroblast growth factor receptor (FGFR) alterations, as common oncogenic drivers in UC, have been reported to drive T cell depletion of UC immune microenvironment via up-regulating FGFR signaling, which indicated FGFR alterations potentially result in reduced response to ICIs. In addition, the selective pan-FGFR inhibitor showed better clinical benefit in clinical trials, indicating FGFR has emerged as critical therapeutic target via inhibiting FGFR signaling. The present study aims to evaluate prognosis and response to ICIs between FGFR-altered UC patients and FGFR-wildtype UC patients via 1963 UC patients and offers new insights into personalized precision therapy and combination therapy for UC. [Display omitted] •FGFR-altered UC patients, especially FGFR3-altered, were more likely to carry worse OS and lower disease control rate in comparison to FGFR-wildtype patients.•Patients receiving maintenance immunotherapy or 2nd-line immunotherapy after 1st-line therapy rather than 1st-line or neoadjuvant immunotherapy were more likely to be influenced by FGFR alterations.•FGFR-altered UC might benefit more from combination of FGFRi and immunotherapy than monotherapy alone.