Introduction: The recent approval of erdafitinib and the emergence of other potent and selective fibroblast growth factor receptor (FGFR) inhibitors (FGFRi’s) are shifting the treatment paradigm for patients with advanced urothelial carcinoma (UC) harboring FGFR3 alterations. Whether such therapies can, and should, be combined with immune checkpoint inhibitors (ICI’s) is an area of major research interest.

Areas covered: Herein, we review the FGFR signaling pathway and impact of altered FGFR signaling on UC tumorigenesis, the clinical development of FGFRi’s, the rationale for FGFRi-ICI combinations, current trials, and future directions.

Expert opinion: FGFR3 altered UCs are not less responsive to ICI’s compared with FGFR3 wild-type (WT) tumors. However, FGFR3 altered tumors may exhibit distinct immunobiology compared with WT tumors that could potentially be exploited therapeutically. Given these considerations along with the clinical non-cross resistance of these therapeutic classes, clinical investigation of regimens combining FGFR3i and ICI is warranted.

简介：erdafitinib的最新批准以及其他有效的和选择性的成纤维细胞生长因子受体（FGFR）抑制剂（FGFRi's）的出现正在改变具有FGFR3改变的晚期尿路上皮癌（UC）患者的治疗模式。这种疗法是否可以并且应该与免疫检查点抑制剂（ICI's）结合是一个主要研究领域。

涵盖的领域：本文中，我们综述了FGFR信号通路以及FGFR信号改变对UC肿瘤发生的影响，FGFRi的临床发展，FGFRi-ICI组合的原理，当前的试验以及未来的方向。

专家意见：与FGFR3野生型（WT）肿瘤相比，FGFR3改变的UC对ICI的反应并不差。然而，与可能被治疗利用的野生型肿瘤相比，FGFR3改变的肿瘤可能表现出独特的免疫生物学特性。考虑到这些考虑因素以及这些治疗类型的临床非交叉耐药性，必须对结合使用FGFR3i和ICI的方案进行临床研究。