Erdafitinib on par with pembrolizumab in metastatic urothelial cancer

Treatment with erdafitinib or pembrolizumab results in similar median overall survival (OS) in pretreated patients with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor (FGFR) alterations (FGFRalt), a study has shown. Safety results are also comparable to the known profiles for both regimens in this patient population.

Notably, pembrolizumab shows better-than-expected outcomes, which are consistent with previous reports in non-FGFR‒altered populations.

In this phase III trial, patients aged ≥18 years with unresectable advanced/mUC, with select FGFRalt, disease progression on prior treatment, and who were antiprogrammed death-(ligand) 1 (anti‒PD-[L]1), were randomly assigned to receive either erdafitinib 8 mg once daily with pharmacodynamically guided uptitration (n=175) to 9 mg or pembrolizumab 200 mg every 3 weeks (n=176).

OS was the primary endpoint, while secondary ones were progression-free survival (PFS), objective response rate (ORR), and safety.

Over a median follow-up of 33 months, no statistically significant difference in OS was observed between erdafitinib and pembrolizumab (median, 10.9 vs 11.1 months; hazard ratio [HR], 1.18, 95 percent confidence interval [CI], 0.92‒1.51; p=0.18).

Median PFS was 4.4 months with erdafitinib and 2.7 months with pembrolizumab (HR, 0.88, 95 percent CI, 0.70‒1.10). The corresponding ORR was 40.0 percent and 21.6 percent (relative risk, 1.85, 95 percent CI, 1.32‒2.59), and the median duration of response was 4.3 and 14.4 months, respectively.

In terms of safety, one or more grade 3‒4 adverse events (AEs) occurred in 64.7 percent of patients treated with erdafitinib and 50.9 percent of those who received pembrolizumab. AEs leading to death were reported in five (2.9 percent) and 12 (6.9 percent) patients, respectively.

“Erdafitinib is an oral pan-FGFR tyrosine kinase inhibitor approved to treat locally advanced/mUC in patients with susceptible FGFRalt who progressed after platinum-containing chemotherapy,” the authors said. “FGFR-altered tumours are enriched in luminal 1 subtype and may have limited clinical benefit from anti–PD-(L)1 treatment.”