Efficacy of erdafitinib before or after enfortumab vedotin in FGFR3-altered advanced urothelial cancer: Analysis of the UNITE collaborative study

Abstract

Background Erdafitinib is approved for locally advanced/metastatic urothelial cancer (LA/mUC). As enfortumab vedotin (EV) plus pembrolizumab enters frontline management, outcomes with erdafitinib pre- and post-EV are clinically relevant but not specifically evaluated in clinical trials. Methods UNITE is a multi-institutional retrospective study of patients with LA/mUC treated with novel targeted agents. All patients with FGFR3 alterations treated with EV only, erdafitinib then EV (Erda->EV), and EV then erdafitinib (EV->Erda) were included. Sequential treatment with EV and Erda was not required. Primary endpoints were observed response rates (ORR) and progression-free survival (PFS); secondary endpoint was overall survival (OS). Results We identified 83 patients with FGFR3 alterations and separated them into three cohorts: EV only (n = 44), Erda->EV (n = 24), and EV->Erda (n = 15). Most (72%) received ≥2 lines of therapy before erdafitinib (checkpoint inhibitor [87%], platinum-based chemotherapy [64%]). Median PFS with erdafitinib for EV-naïve cohort was 7.5 months and in EV-treated cohort 4.0 months (HR 0.78; 95% CI 0.35-1.7). ORR with erdafitinib for EV-naïve was 33% and EV-treated 31% (OR 1.1; 95% CI 0.29-4.1). Median PFS with EV for patients who were erdafitinib-naïve was 6 months and in erdafitinib-treated 5.3 months (HR 0.61; 95% CI 0.34-1.09). ORR with EV was 54% in erdafitinib-naïve cohort and 32% in erdafitinib-treated cohort (OR 2.5; 95% CI 0.87-6.3). Conclusion In patients with FGFR3-altered LA/mUC, erdafitinib is active pre- and post-EV. Outcomes with erdafitinib were consistent with clinical trial data generated prior to broader frontline use of EV. Findings are hypothesis-generating and given small sample size should be interpreted with caution.