Clinical outcomes for patients (pts) with synchronous versus metachronous metastatic urothelial cancer (mUC) treated with enfortumab vedotin and pembrolizumab (EV-P).

Abstract

4587 Background: Synchronous versus metachronous metastases in mUC has prognostic significance, and EV-P has emerged as standard first-line therapy for pts with mUC. How primary disease in synchronous mUC should be best treated remains unclear. This study evaluated clinical outcomes of pts with synchronous vs metachronous mUC treated with EV-P. Methods: A retrospective analysis of all consecutive pts with mUC treated EV–P at UTSW was performed. Patients were grouped by synchronous mUC or metachronous mUC. Baseline characteristics were compared using Wilcoxon rank-sum and Chi-squared tests. Overall survival (OS) and progression-free survival (PFS) were analyzed using Cox proportional hazards models. Results: For 159 pts with mUC treated with EV-P between 9/2020 and 12/2025, 40 had synchronous mUC and 119 had metachronous mUC. Baseline characteristics were similar with median age 71.5 years vs 73.0 years (p=0.90), male 75% vs 94%(p=0.76), and visceral metastases (20% vs 26%, p=0.58). In metachronous mUC, 76 (63.9%) had prior cystectomy and 42 (35.3%) had prior radiation as definitive treatment. Patients with metachronous mUC demonstrated a median PFS of 16.0 months vs not reached (NR) for patients with synchronous mUC (HR 1.95, 95% CI 1.05–3.62; p = 0.035). Similarly, the median OS was 21.9 months for metachronous mUC vs not reached in the synchronous mUC (HR 2.61, 95% CI 1.24–5.49; p = 0.011). Median cycles of EV-P was 13.5 for synchronous mUC vs 10 for metachronous mUC. For synchronous mUC, 22 (55.0%) underwent cystectomy and 8 (20.0%) underwent radiation as consolidative treatment. Conclusions: Synchronous and metachronous mUC treated with EV-P have significantly different disease courses on EV-P. Metachronous mUC has earlier progression on EV-P, needing more treatment options in refractory disease. Consolidation treatment for synchronous mUC needs further prospective trials for optimal outcomes. Comprehensive baseline characteristics and clinical outcomes. Characteristic Synchronous met Metachronous met P value Number of patients 40 119 Age at treatment initiation, median (IQR) 71.5 (64.5–76.0) 73.0 (64.0–78.0) 0.904 Male sex, n (%) 30 (75.0%) 94 (79.0%) 0.759 Prior local therapy Prior radical cystectomy N/A 76 (63.9%) Prior radiation therapy N/A 42 (35.3%) Metastatic burden Any visceral metastasis 8 (20.0%) 31 (26.1%) 0.578 Liver metastasis 6 (15.0%) 17 (14.3%) 1.000 Treatment and outcomes EV-P cycles, median (range) 13.5 (1–39) 10.0 (1–57) 0.281