Clinical Development of FGFR3 Inhibitors for the Treatment of Urothelial Cancer

The fibroblast growth factor receptor 3 (FGFR3) plays critical roles in driving oncogenesis of a subset of patients with urothelial carcinomas (UC). Growing evidence from preclinical studies suggests that FGFR3 inhibition can reduce proliferation and survival in vitro and in vivo models of FGFR3-altered UC. Early clinical trials investigating selective FGFR3 inhibitor have reported preliminary signs of antitumor activity in advanced UC patients with selected FGFR3 mutations or fusions. Currently, phase 3 trials with erdafitinib and rogaratinib are enrolling patients with known FGFR3 alterations. Future combinations with targeted therapies or immune checkpoint inhibitors may increase the efficacy of selective FGFR3 inhibitors. Herein, we discuss current clinical development of FGFR3 inhibitors as well as unsolved questions with regards to patient selection, management of toxicities and mechanisms of resistance to selective FGFR3 inhibitors.