Fibroblast growth factor (FGF) signaling contributes to tumorigenesis in a wide variety of tumor types. In metastatic urothelial cancer (mUC), mutations of the FGF receptor can be found in about 20% of cases. This abstract discusses two phase III trials currently recruiting UC patients in Belgium using the FGF-R targeting agents rogaratinib (BAY-1163877) and erdafitinib (JNJ-42756493).

Materials and methods

The protocols of both studies were analyzed to identify targeted unmet medical needs in the treatment of mUC.


Erdafitinib is a strong pan-FGF-R inhibitor that showed significant inhibition of proliferation in preclinical trials. In a large phase I study (N=187) of mUC patients with FGF-R aberrations, overall response rate (ORR)was 40%, 70% in higher doses. The most frequent adverse events (AE) were hyperphosphatemia, dry mouth, asthenia and stomatitis. The current randomized open label phase III trial(NCT03390504) compares single agent erdafitinib to chemotherapy (investigators choice) in patients with prior anti-PD(L)1 treatment in one cohort and to pembrolizumab in patients without prior anti-PD(L)1 treatment in the second cohort. The primary endpoint is overall survival (OS).

Rogaratinib is a strong pan-FGF-R targeting TKI that also showed strong inhibition of cell growth in preclinical models. Two phase I trials have studied rogaratinib. Tolerance was good with hyperphosphatemia, fatigue and gastro-intestinal symptoms as main AEs. As with other FGF-R inhibitors, retinal disorder is a treatment limiting toxicity. The current open label study randomizes mUC patients to rogaratinib and second line chemotherapy (docetaxel, paclitaxel or vinflunin) in patients with tumors expressing FGF-R mutations or high mRNA load. The phase II part will randomize 58 patients in each arm, the study is planned to continue in a phase III after a futility analysis. Primary endpoint in phase II is ORR, in phase III OS.


Treatment of mUC patients after progression on platinum based chemotherapy and eventually checkpoint inhibitors is an unmet need. Both rogaratinib and erdafitinib are effective in targeting FGF-R mutations in a subgroup of patients and have shown high ORR in phase I studies. Phase III trials are open to recruitment and offer mUC patients a biomarker-based alternative to poorly active second line cytotoxic therapy.