What is Erdafitinib? Erdafitinib is a small-molecule, orally administered kinase inhibitor that selectively targets fibroblast growth factor receptors (FGFR). Approved by the US FDA in 2019 under the brand name Balversa, it was the first FGFR-targeted therapy approved for metastatic urothelial carcinoma. It represents a significant advancement in precision oncology, offering a targeted option for patients whose tumors harbor specific FGFR genetic alterations. Erdafitinib is used as a second-line therapy for patients with advanced or metastatic bladder cancer who have progressed during or following platinum-based chemotherapy. Treatment initiation is strictly guided by the presence of companion diagnostic-confirmed FGFR3 or FGFR2 mutations or fusions. Mechanism of Action Fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3, and FGFR4) are transmembrane receptor tyrosine kinases that play a key role in cell proliferation, survival, migration, and angiogenesis. In several cancers, particularly urothelial carcinoma, genetic alterations such as mutations, fusions, or amplifications lead to constitutive activation of FGFR signaling. This drives uncontrolled tumor growth and survival through downstream pathways, including the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. Erdafitinib is an inhibitor of FGFR tyrosine kinase activity. It binds to the ATP-binding pocket of FGFR1-4, blocking receptor autophosphorylation and downstream signal transduction. By inhibiting FGFR signaling, Erdafitinib decreases cell viability and induces apoptosis in tumor cell lines that express FGFR genetic alterations. It also demonstrates anti-tumor activity in vivo in FGFR-expressing xenograft models. Pharmacokinetics & Administration Following oral administration, Erdafitinib is absorbed, with median peak plasma concentrations (Tmax) achieved within 2.5 hours. It can be taken with or without food, as food does not cause clinically significant changes in its overall exposure. Erdafitinib is highly bound to plasma proteins (99.6%), primarily to alpha-1-acid glycoprotein. The steady-state volume of distribution is approximately 29 liters. Erdafitinib is metabolized primarily in the liver by cytochrome P450 enzymes CYP2C9 and CYP3A4. The terminal elimination half-life is approximately 59 hours, allowing for once-daily dosing. Elimination occurs primarily through feces (69%, mostly as metabolites) and urine (19%, as metabolites). Due to its metabolism via CYP2C9 and CYP3A4, co-administration with strong inhibitors or inducers of these enzymes requires dose adjustments or avoidance. Clinical Indications & Dosage Erdafitinib is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma that has susceptible FGFR3 or FGFR2 genetic alterations, and who have progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. The standard starting dosage is 8 mg taken orally once daily, at the same time each day, with or without food. Based on individual tolerability and serum phosphate levels measured between day 14 and 21 of treatment, the dose may be escalated to a maximum of 9 mg once daily. Hyperphosphatemia is a pharmacodynamic marker of FGFR inhibition, and achieving target serum phosphate levels (between 5.5 and 7.0 mg/dL) is critical for optimal efficacy. Warnings & Safety warnings Erdafitinib is associated with class-specific toxicities due to FGFR inhibition: Ocular Toxicities: Erdafitinib can cause central serous retinopathy (CSR) or retinal pigment epithelial detachment (RPED), leading to blurred vision, dry eyes, or visual field defects. Regular ophthalmic examinations, including optical coherence tomography (OCT), are required before starting and periodically during treatment. Hyperphosphatemia: Elevated serum phosphate levels occur in most patients due to FGFR inhibition in the kidneys, which blocks phosphate excretion. Dietary phosphate restriction and oral phosphate binders may be required. Skin and Nail Toxicity: Common dermatologic effects include dry skin, hand-foot syndrome, nail loss, and painful nail bed disorders. Proper moisturizing and protective nail care are recommended. Frequently Asked Questions What are the signs of ocular toxicity I should watch for? Patients taking Erdafitinib should report any visual changes—such as blurred vision, flashes of light, floaters, or dark spots—to their oncologist immediately. Treatment should be suspended if central serous retinopathy is diagnosed. Why are my phosphate levels monitored? FGFR receptors regulate phosphate reabsorption in the kidneys. Blocking these receptors leads to increased phosphate levels in the blood. Monitoring helps determine the correct dose and guides the use of phosphate binders.