Clinical Evidence and Selecting Patients for Treatment with Erdafitinib in Advanced Urothelial Carcinoma

Area of Science:

• Oncology
• Pharmacology
• Genetics

Background:

• Erdafitinib is a targeted therapy approved for metastatic or locally advanced urothelial carcinoma (UC) with specific fibroblast growth factor receptor (FGFR) alterations.
• It was the first targeted therapy to receive accelerated FDA approval for metastatic bladder cancer.
• Patients must have progressed on at least one platinum-based chemotherapy regimen.

Purpose of the Study:

• To evaluate the efficacy and safety of erdafitinib in patients with advanced UC and susceptible FGFR alterations.
• To identify potential pharmacodynamic markers of response to erdafitinib.
• To inform ongoing and future clinical trials, including the Phase III THOR study.

Main Methods:

• The BLC2001 trial, a single-arm study, evaluated erdafitinib in patients with advanced UC and FGFR alterations.
• Overall response rate (ORR) was a primary efficacy endpoint.
• Adverse events were monitored, and serum phosphate levels were analyzed as a pharmacodynamic marker.

Main Results:

• Erdafitinib demonstrated an overall response rate of 40% in the BLC2001 trial.
• Common adverse events included hyperphosphatemia and retinopathy, necessitating regular monitoring.
• Increased serum phosphate levels were identified as a pharmacodynamic marker of response.

Conclusions:

• Erdafitinib shows significant efficacy in a subset of patients with advanced UC harboring FGFR alterations.
• Hyperphosphatemia serves as a pharmacodynamic marker, but further biomarker investigations are warranted.
• Ongoing trials like THOR are crucial for full approval, and optimal sequencing with other therapies remains an unmet need.