Erdafitinib, marketed as Balversa, has emerged as a targeted therapy for adult patients with locally advanced or metastatic urothelial carcinoma (mUC) harboring fibroblast growth factor receptor 3 (FGFR3) genetic alterations. This approval is specifically for patients who have progressed on or after at least one line of prior systemic therapy. It is not recommended for patients eligible for PD-1 or PD-L1 inhibitors who have not yet received such therapy.
Pivotal Clinical Trials
The efficacy and safety of erdafitinib are supported by several clinical trials. The BLC2001 (NCT02365597) Phase 2 study, a multicenter, open-label, single-arm trial, evaluated erdafitinib in 87 patients with locally advanced or mUC who had progressed on at least one line of prior platinum-based chemotherapy and had tumors with at least one FGFR mutation. The objective response rate (ORR) was 32.2%, including patients who had previously not responded to anti-PD-L1/PD-1 therapy. The median duration of response (DoR) was 5.4 months.
The BLC3001 (THOR) Cohort 1 study, a randomized, open-label, multicenter, Phase 3 trial, compared erdafitinib versus chemotherapy in 266 patients with mUC with FGFR3 alterations who had progression after one or two previous lines of therapy that included an anti-PD-1 or anti-PD-L1 agent. Patients were randomized 1:1 to receive erdafitinib or investigator's choice of chemotherapy (docetaxel or vinflunine). The primary endpoint was overall survival (OS). Results showed improved OS (12.1 months versus 7.8 months), progression-free survival (PFS) (5.6 months versus 2.7 months), and overall response rate (ORR) (35.3% versus 8.5%) in the erdafitinib arm.
In contrast, the BLC3001 (THOR) Cohort 2 study, a multicenter, open-label, randomized trial of 351 patients with locally advanced or mUC with FGFR3 alterations who had received one prior line of systemic therapy and no prior PD-1 or PD-L1 inhibitor, did not meet its primary endpoint of OS superiority when comparing erdafitinib to pembrolizumab (median 10.9 months versus 11.1 months, respectively).
Mechanism of Action and Dosing
Erdafitinib functions as an oral kinase inhibitor of FGFR, targeting FGFR gene alterations involved in the deregulation of proliferation of certain tumor cells. The recommended initial dosage is 8 mg orally once daily, with a potential dose increase to 9 mg daily based on tolerability and hyperphosphatemia. Serum phosphate levels should be assessed 14-21 days after initiating treatment, and the dose may be increased to 9 mg if the phosphate level is less than 9.0 mg/dL, provided there are no ocular disorders or grade >2 adverse events. Erdafitinib is available in 3, 4, and 5 mg tablets and should be swallowed whole, with or without food. Treatment should continue until disease progression or unacceptable toxicity.
Warnings, Precautions, and Adverse Reactions
Ocular events, particularly central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED), are a significant concern with erdafitinib. Baseline and monthly ophthalmologic evaluations are recommended for the first four months of treatment, followed by evaluations every three months or with any visual changes. Erdafitinib should be withheld if CSR/RPED occurs and permanently discontinued if not resolved within four weeks or if grade 4 severity is observed.
Hyperphosphatemia is an expected on-target effect of erdafitinib, necessitating monitoring of phosphate levels and appropriate dose modifications. The most common (≥20%) adverse reactions associated with erdafitinib include increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphatase (ALP), increased alanine aminotransferase (ALT), decreased hemoglobin, decreased sodium, increased aspartate aminotransferase (AST), fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, taste changes, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy.
Patients should restrict phosphate intake to 600-800 mg daily. For CSR, erdafitinib should be withheld, and an ophthalmic evaluation should be obtained within two weeks. For other adverse events, erdafitinib should be held for grade 3 AEs until resolution to grade 1, then resumed with a dose reduction. Permanent discontinuation is recommended for any grade 4 AE.
Essential Patient Information
Prior to initiating treatment with erdafitinib, confirmation of the presence of FGFR3 genetic alterations in tumor specimens is mandatory. Patients should be advised to notify their oncology care team of any visual changes, progressive skin, mucous, or nail changes, or symptoms associated with acute hyperphosphatemia, such as muscle cramps or numbness around the mouth. Female patients of childbearing potential should undergo a pregnancy test before starting erdafitinib and use effective birth control during and for one month after discontinuation. Male patients with female partners who may become pregnant should also use effective birth control during and for one month after the last dose of erdafitinib. Breastfeeding is contraindicated during treatment and for one month after completion of erdafitinib.
Nursing Considerations
If a dose is missed, it can be taken as soon as possible on the same day, resuming the daily dosing schedule the following day. Concomitant use of strong CYP3A4 inducers should be avoided; moderate CYP3A4 inducers should be given with erdafitinib at a dose of 9 mg daily. Consider alternate medications or monitor closely for adverse side effects when used with moderate CYP2C9 or strong CYP3A4 inhibitors. P-gp substrates should be separated by at least 6 hours before or after administration of erdafitinib. Erdafitinib should be stored at room temperature and kept out of reach of children.
