First Targeted Smart Drug Approved for Bladder Cancer: Erdafitinib

For patients carrying FGFR3 or FGFR2 genetic alterations who had previously received platinum -based chemotherapy and had locally advanced or metastatic urothelial (bladder and urinary tract) cancer, erdafitinib (Balversa) received FDA approval on 12 April 2019. The approval also includes patients who received, within 12 months, neoadjuvant or adjuvant platinum-based chemotherapy.

For erdafitinib to be used, patients with bladder cancer must be shown to be positive for FGFR2 and FGFR3 genetic alterations using the therascreen® FGFR RGQ RT-PCR kit, also approved by the FDA.

The approval of erdafitinib was based on BLC2001, a multicenter, open-label, single-arm clinical trial, and data from 87 enrolled patients. These patients had locally advanced or metastatic urothelial cancer that had progressed after at least 1 previous line of chemotherapy and had specific FGFR3 gene mutations or FGFR2 or FGFR3 gene fusions. Patients received an initial dose of 8 mg of erdafitinib daily; on days 14-17, patients with serum phosphate levels below 5.5 mg/dL had their dose increased to 9 mg daily. In % 41 of patients, the dose was increased to 9 mg. Erdafitinib was administered until disease progression or unacceptable adverse effects occurred.

Study Results

• The main efficacy outcome measure the study aimed to assess was the objective radiological response rate, as determined by a blinded independent review committee.
• Of the patients, % 32.2 had an objective response to treatment; % 2.3 of these responses were complete responses and % 29.9 were partial responses.
• The median response duration was 5.4 months. Responders also included patients previously treated with anti PD-L1 or PD-1 immunotherapies who had not responded.

Erdafitinib can cause ocular (eye) disorders. Central serous retinopathy or retinal pigment epithelial detachment resulting in visual field defects was reported in % 25 of patients. The most common adverse effects reported in at least % 40 of patients were increased serum phosphate, stomatitis, fatigue, increased serum creatinine, diarrhea, dry mouth, onycholysis (nail separation), increased ALT, increased alkaline phosphatase, and decreased sodium.

The recommended initial dose of erdafitinib is 8 mg orally once daily (with or without food); if the criteria are met, an increase to 9 mg daily is recommended.