Erdafitinib is a pan-FGFR tyrosine kinase inhibitor of FGFR1-4 that has been tested in a phase II trial in 99 patients with locally advanced or metastatic previously treated UC and FGFR DNA genomic alterations...Erdafitinib is recommended in platinum-refractory tumours with FGFR alterations.

The primary endpoint of the study was met, with erda significantly increasing OS and reducing the risk of death by 36%; median OS was 1 y...Erda also significantly improved median PFS (5.6 vs 2.7 mo) and ORR (46% vs 12%) vs chemo….In pts with FGFRalt advanced/mUC after prior treatment with PD-(L)1, erda significantly improved OS, PFS, and ORR vs investigator’s choice of chemo. Erda toxicity was consistent with the known safety profile. These results support the role of erda to treat pts with FGFRalt mUC after PD-(L)1 tx.

...- Participants must meet the following molecular eligibility criteria (diagnosed at a central or local laboratory using either a tumor tissue based assay, which must indicate: at least one of following): a) fibroblast growth factor receptor (FGFR) gene translocations b) FGFR gene mutations c) Participants with evidence of FGFR pathway activation or other potential target/pathway inhibited by erdafitinib may also be considered and allowed for enrollment if supported by emerging biomarker data....

We aimed to assess the long-term efficacy and safety of the selected regimen of erdafitinib determined in the initial part of the study....Eligible patients were aged 18 years or older with locally advanced and unresectable or metastatic urothelial carcinoma, at least one prespecified FGFR alteration....Median efficacy follow-up was 24·0 months (IQR 22·7–26·6). The investigator-assessed objective response rate for patients treated with the selected erdafitinib regimen was 40 (40%; 95% CI 30–49) of 101 patients.

With a median follow-up of 2 yrs, ERDA in mUC + FGFR alt showed a manageable safety profile and consistent efficacy, with median OS of 11.3 mos. 31% had a DOR ≥12 mos and 31% were alive at 24 mos.

All patients with urothelial carcinoma and cholangiocarcinoma who responded to erdafitinib carried FGFR mutations or fusions. The ORR in the all treated urothelial carcinoma population was 12 of 30 (40%), and 12 of 26 (46%) in the FGFR mutation and fusion-positive population. For urothelial carcinoma patients, 10 were treated with continuous dosing (9 mg daily), and 16 were treated with intermittent schedule (15 at 10 mg and 1 at 12 mg) and the response rate was numerically higher at 70% with 9 mg daily than 32% with intermittent dosing (Table 4; Fig. 1A).