Association between hyperphosphatemia and overall survival among patients with advanced urothelial cancer treated with erdafitinib in phase 2/3 clinical trials

BACKGROUND: Hyperphosphatemia is a recognized on-target adverse event of erdafitinib, a pan-fibroblast growth factor receptor (pan-FGFR) tyrosine kinase inhibitor with Food and Drug Administration approval to treat advanced urothelial cell carcinoma with FGFR2/3 mutations. This study hypothesized that hyperphosphatemia is a biomarker for drug activity and is associated with improved overall survival (OS) and other oncologic end points in phase 2/3 clinical trials. METHODS: Data from the phase 2 BLC2001 and cohorts 1 and 2 of the phase 3 THOR clinical trials were pooled; only patients who received erdafitinib were included. Kaplan-Meier and Cox proportional hazards models were used to examine the effect of hyperphosphatemia (as classified by Common Terminology Criteria for Adverse Events [CTCAE] grade) on OS, progression-free survival (PFS), and objective response rate (ORR). RESULTS: A total of 409 subjects (median age, 66 years; interquartile range, 60-72 years) who met the inclusion criteria were pooled from the THOR and BLC2001 clinical trials, of whom 78.4% had hyperphosphatemia. Subjects with CTCAE grade 3+ hyperphosphatemia had improved OS (hazard ratio [HR], 0.21; 95% CI, 0.05-0.86; p = .031) and PFS (HR, 0.16; 95% CI, 0.04-0.67; p = .012) in multivariable Cox proportional hazards models compared to patients without hyperphosphatemia. CONCLUSIONS: In this secondary analysis of the BLC2001 and THOR trials, higher CTCAE hyperphosphatemia grades were associated with improved OS, PFS, and ORR. These findings suggest that hyperphosphatemia may serve as a potential biomarker of erdafitinib activity, and warrant prospective validation.