On January 19, the U.S. Food and Drug Administration (FDA) approved the FGFR inhibitor erdafitinib (Balversa) for adult patients with locally advanced or metastatic urothelial carcinoma 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. This approval amends the indication previously granted under accelerated approval for patients with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 or FGFR2 alterations after prior platinum-containing chemotherapy.
THOR/Study BLC3001
The efficacy of erdafitinib was evaluated in Study BLC3001 (THOR; ClinicalTrials.gov identifier NCT03390504) Cohort 1, a randomized, open-label trial of 266 patients with locally advanced or metastatic urothelial carcinoma harboring selected FGFR3 alterations who had received one to two prior systemic treatments, including a PD-1 or PD-L1 inhibitor. Patients were randomly assigned 1:1 to receive erdafitinib or investigator’s choice of chemotherapy (docetaxel or vinflunine). Random assignment was stratified by region, performance status, and presence of visceral or bone metastases.
FGFR3 alterations were identified from tumor tissue in a central laboratory by the therascreen FGFR RGQ RT-PCR kit (Qiagen) in 75% of patients. The remainder were identified by local next-generation sequencing assays.
The major efficacy outcome measure was overall survival. Investigator-assessed progression-free survival and objective response rate were additional outcome measures.
Statistically significant improvements in overall survival, progression-free survival, and objective response rate were demonstrated for erdafitinib compared with chemotherapy. Median overall survival was 12.1 months (95% confidence interval [CI] = 10.3–16.4 months) for patients who received erdafitinib and 7.8 months (95% CI = 6.5–11.1 months) for those who received chemotherapy (hazard ratio [HR] = 0.64, 95% CI = 0.47–0.88, P = .0050). Median progression-free survival was 5.6 months (95% CI = 4.4–5.7 months) for patients who received erdafitinib and 2.7 months (95% CI = 1.8–3.7 months) for those who received chemotherapy (HR = 0.58, 95% CI = 0.44–0.78, P = .0002). The confirmed objective response rate 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 < .001).
The most common (occurring in > 20% of patients receiving erdafitinib) adverse reactions, including laboratory abnormalities, 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 to 21 days. Treatment should continue until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 6 weeks ahead of the FDA goal date. This application was also granted Priority Review.
