The U.S. Food and Drug Administration (FDA) recently granted full approval to Balversa (erdafitinib) for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) who have susceptible FGFR3 gene alterations and whose disease has progressed after at least one prior systemic therapy. This drug is an oral FGFR kinase inhibitor that received accelerated approval from the FDA in 2019.
Notably, Balversa is the first approved oral FGFR kinase inhibitor and the first and only targeted therapy for patients with metastatic urothelial carcinoma and FGFR alterations.
The efficacy of Balversa is supported by data from the Phase 3 THOR study (NCT03390504), which compared Balversa with standard-of-care chemotherapy (investigator-selected docetaxel or vinflunine). Group 1 included 266 adults with advanced urothelial carcinoma and selected FGFR3 alterations.
All patients had experienced disease progression after one or two prior lines of therapy, with at least one line including a programmed death receptor 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor. The primary efficacy endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
Results showed that Balversa treatment reduced the risk of death by 36% compared to chemotherapy (hazard ratio [HR], 0.64 [95% CI, 0.47–0.88]; P = 0.005). The median OS was 12.1 months in the Balversa group and 7.8 months in the chemotherapy group.
The median PFS was 5.6 months in the Balversa group and 2.7 months in the chemotherapy group (HR, 0.58 [95% CI, 0.44–0.78; P = 0.0002]. The ORR in the Balversa group was 35.3% (5.1% complete response, 30.1% partial response), while the ORR in the chemotherapy group was 8.5% (0.8% complete response, 7.7% partial response).
Patient selection should be based on the presence of susceptible FGFR3 gene alterations in tumor specimens detected by FDA-approved companion diagnostics. Balversa is not recommended for the treatment of eligible patients who have not previously received PD-1 or PD-L1 inhibitor therapy.
The most common (>20%) adverse reactions (including laboratory abnormalities) were elevated phosphate, nail abnormalities, diarrhea, stomatitis, elevated alkaline phosphatase, decreased hemoglobin, elevated alanine aminotransferase, elevated aspartate aminotransferase, decreased sodium, elevated creatinine, dry mouth, decreased phosphate, palmoplantar paresthesia syndrome, taste disturbance, fatigue, dry skin, constipation, decreased appetite, elevated calcium, alopecia, dry eyes, elevated potassium, and weight loss.
The recommended dose of erdafitinib is 8 mg orally once daily, increasing to 9 mg once daily at 14 to 21 days based on tolerability (including hyperphosphatemia). Treatment should continue until disease progression or unacceptable toxicity.
