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.