Platinum-based chemotherapy after enfortumab vedotin and pembrolizumab in metastatic urothelial carcinoma: a real-world study

BACKGROUND: Platinum-based chemotherapy (PBC) is frequently used after first-line enfortumab vedotin-pembrolizumab for metastatic urothelial carcinoma (mUC), yet efficacy in this setting remains undefined. PATIENTS AND METHODS: We retrospectively reviewed an institutional database of 236 patients with mUC treated with enfortumab vedotin-pembrolizumab between October 2018 and December 2024 to identify those receiving second-line PBC. Responses were investigator-assessed. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of PBC; duration of response (DOR) was estimated from the first documented response. RESULTS: Of 62 patients treated with subsequent systemic therapy, 74% (n = 46) received PBC (carboplatin, n = 34; cisplatin, n = 12); nine patients (20%) then received maintenance avelumab. Median age was 73 years; 65% were male; 30% had upper-tract primary. Objective response rate (ORR) to first-line enfortumab vedotin-pembrolizumab was 41%. Median follow-up was 11 months [95% confidence interval (CI) 9.2-not reached (NR)]. ORR to second-line PBC was 49% (22 of 45, 95% CI 34% to 64%), including two complete responses; median DOR was 5.2 months (95% CI 3.8-NR). Median PFS was 5 months (95% CI 3.6-6.6), and median OS was 12 months (95% CI 10-17). Outcomes did not differ between cisplatin and carboplatin (P > 0.9). CONCLUSIONS: In a real-world setting, PBC after enfortumab vedotin-pembrolizumab demonstrated meaningful activity but modest durability. These findings may inform clinical management and future trial design.