Background
Open-label phase II trial (BLC2001) of 99 patients with locally advanced and unresectable or metastatic urothelial carcinoma harboring FGFR3 or FGFR2 alterations, previously treated with chemotherapy; prior immunotherapy was allowed.
Interventions and follow up
Regimen: Erdafitinib 8 mg PO once daily, with pharmacodynamically guided up-titration to 9 mg
Primary endpoint: Objective response rate (ORR)
Median follow up: 11.2 mo
Primary endpoint: Objective response rate (ORR)
Median follow up: 11.2 mo
Results
Confirmed ORR: 40%
Median duration of response: 5.6 mo
mPFS: 5.5 mo
mOS: 13.8 mo
Median duration of response: 5.6 mo
mPFS: 5.5 mo
mOS: 13.8 mo
Adverse events
Grade 3 or higher events: Hyponatremia 11%; stomatitis 10%; asthenia 7%; urinary tract infection 5%
Dermatologic/FGFR class effects: Nail dystrophy 6%; hand-foot syndrome 5%; central serous retinopathy and hyperphosphatemia reported as class-related toxicities
Dermatologic/FGFR class effects: Nail dystrophy 6%; hand-foot syndrome 5%; central serous retinopathy and hyperphosphatemia reported as class-related toxicities
Conclusions
Erdafitinib produced a high response rate in FGFR-altered locally advanced or metastatic urothelial carcinoma, including in patients with prior immunotherapy.
Key Limitations
Single-arm, non-comparative phase II restricted to FGFR-altered tumors. The randomized THOR trial subsequently confirmed an OS benefit over chemotherapy and refined the population to post-immunotherapy use.
Clinical Context
BLC2001 supported FDA accelerated approval of erdafitinib for FGFR2/3-altered advanced urothelial carcinoma, the first targeted therapy in this disease. The confirmatory THOR trial led to full approval (2024) and supports ASCO/ESMO endorsement of FGFR-directed therapy after prior systemic treatment.