On January 19, 2024, the U.S. Food and Drug Administration (FDA) approved erdafitinib (Balversa®) for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible FGFR3 genetic alterations, as determined by an FDA-approved companion diagnostic test, whose disease has progressed on or after at least one line of prior systemic therapy. Erdafitinib is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy. The approval amends erdafitinib’s previous accelerated approval for patients with mUC with susceptible FGFR3 or FGFR2 alterations after prior platinum-containing chemotherapy.
Efficacy was evaluated in Study BLC3001 Cohort 1, a randomized, open-label trial of 266 patients with mUC harboring selected FGFR3 alterations who had received one or two prior systemic treatments, including a PD-1 or PD-L1 inhibitor. Patients were randomized 1:1 to receive erdafitinib or the investigator’s choice of chemotherapy (docetaxel or vinflunine). Randomization was stratified by region, performance status, and presence of visceral or bone metastases. FGFR3 alterations were identified from tumor tissue in a central laboratory using the therascreen FGFR RGQ RT-PCR kit for 75% of patients and local next-generation sequencing assays for 25% of patients.
The major efficacy outcome measure was overall survival (OS). Investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were additional outcome measures.
Statistically significant improvements in OS, PFS, and ORR were demonstrated for erdafitinib compared with chemotherapy. Median OS was 12.1 months (95% CI = 10.3, 16.4) for patients who received erdafitinib and 7.8 months (95% CI = 6.5, 11.1) for those who received chemotherapy (HR = 0.64 [95% CI = 0.47, 0.88]; p = 0.0050). Median PFS was 5.6 months (95% CI = 4.4, 5.7) for patients who received erdafitinib and 2.7 months (95% CI = 1.8, 3.7) for those who received chemotherapy (HR = 0.58 [95% CI = 0.44, 0.78]; p = 0.0002). Confirmed ORR was 35.3% (95% CI = 27.3, 43.9) for those who received erdafitinib and 8.5% (95% CI = 4.3, 14.6) for those who received chemotherapy (p < 0.001).
The most common adverse reactions, including laboratory abnormalities, reported in more than 20% of the patients in the clinical trial, were increased phosphate, nail disorders, diarrhea, stomatitis, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased aspartate aminotransferase, decreased sodium, increased creatinine, dry mouth, decreased phosphate, palmar-plantar erythrodysesthesia syndrome, dysgeusia, fatigue, dry skin, constipation, decreased appetite, increased calcium, alopecia, dry eye, increased potassium, and decreased weight.
The recommended erdafitinib dose is 8 mg orally once daily, with a dose increase to 9 mg once daily based on tolerability, including hyperphosphatemia, at 14–21 days. Treatment should continue until patients experience disease progression or unacceptable toxicity.
View the full prescribing information for erdafitinib.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved this application six weeks ahead of the goal date. The application was granted priority review. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Office of Oncology Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.