Erdafitinib Receives a New FDA Approval for Advanced Bladder Cancer

On January 19, 2024, the US Food and Drug Administration (FDA) approved erdafitinib (Balversa, Janssen Biotech) for adults with locally advanced or metastatic urothelial carcinoma (urinary tract cancer) with FGFR3 genetic alterations.

Under this new approval, patients must have experienced cancer progression despite at least one previous line of systemic cancer treatment to receive erdafitinib. It is not recommended for patients eligible for PD-1 or PD-L1 immunotherapy who have not yet received it. This latest FDA approval expands the scope of the accelerated approval granted in 2019 for metastatic urothelial carcinoma with FGFR3 or FGFR2 alterations after platinum-based chemotherapy and changes the previously established treatment indications.

What Is Erdafitinib (Balversa), and How Does It Work?

Erdafitinib is a targeted treatment directed at altered fibroblast growth factor receptors (FGFRs) in urothelial cancer cells. Normally, specific extracellular ligands (growth factors) bind to FGFRs, activating them and triggering intracellular signaling pathways that regulate cell growth and proliferation. In some cancer cells, however, FGFR gene alterations, such as gene amplification, chromosomal translocations, alternative splicing events or point mutations, cause persistent ligand-independent FGFR activation and uncontrolled cell proliferation.

By targeting these abnormal FGFRs, erdafitinib blocks intracellular signaling pathways, suppressing cancer cell growth and spread. Balversa (erdafitinib), represented by the green circle in the figure, binds to altered FGFR in the cell membrane and stops signaling, thereby inhibiting cancer cell growth.

FDA Approval Based on the BLC3001 Study

The accelerated approval in 2019 assessed the drug's effectiveness in a more limited patient group with less detailed clinical data. The new approval is based on results from a comprehensive clinical study involving 266 patients.

The new approval is based on BLC3001. Patients were randomized to erdafitinib or chemotherapy (docetaxel or vinflunine). The study found statistically significant improvements with erdafitinib in OS (overall survival), PFS (progression-free survival) and ORR (objective response rate) compared with chemotherapy.

Erdafitinib's effectiveness was evaluated in cohort 1 of BLC3001, involving 266 patients with metastatic urothelial carcinoma (mUC), selected FGFR3 alterations and 1-2 prior lines of systemic therapy, including at least one immunotherapy.

In this randomized, open-label trial, patients were assigned 1:1 to erdafitinib or investigator-selected chemotherapy (docetaxel or vinflunine). Randomization was stratified by region, performance status and the presence of visceral (internal organ) or bone metastases. In 75% of patients, FGFR3 alterations were detected centrally using the therascreen FGFR RGQ RT-PCR kit (Qiagen); local next-generation sequencing tests were used for the remaining patients.

The primary efficacy outcome was overall survival (OS). Other outcomes included investigator-assessed progression-free survival (PFS) and objective response rate (ORR).

Erdafitinib demonstrated statistically significant improvements in OS, PFS and ORR compared with chemotherapy.

Results

• Median OS among patients receiving erdafitinib was 12.1 months (95 percent confidence interval: 10.3, 16.4), compared with 7.8 months for chemotherapy (95 percent confidence interval: 6.5, 11.1) (hazard ratio [HR] 0.64 [95 percent confidence interval: 0.47, 0.88]; p-value=0.0050).
• Median PFS among patients receiving erdafitinib was 5.6 months (95 percent confidence interval: 4.4, 5.7), compared with 2.7 months for chemotherapy (95 percent confidence interval: 1.8, 3.7) (HR 0.58 [95 percent confidence interval: 0.44, 0.78]; p-value=0.0002).
• The confirmed ORR among patients receiving erdafitinib was 35.3% (95 percent confidence interval: 27.3, 43.9), compared with 8.5%for chemotherapy (95 percent confidence interval: 4.3, 14.6) (p-value<0.001).

The most common (> 20%) adverse reactions and laboratory abnormalities included 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. Depending on tolerability, including hyperphosphatemia, it may be increased to 9 mg once daily within 14 to 21 days. Treatment should continue until disease progression or unacceptable toxicity.