• This multicenter real-world study describes treatment sequencing and outcomes in metastatic urothelial carcinoma before the widespread use of enfortumab vedotin-based combinations. • Platinum-based chemotherapy followed by avelumab maintenance achieved a median overall survival of 29 months in selected patients. • High attrition rates were observed between treatment lines, limiting access to subsequent therapies in routine practice. • Patients with ECOG performance status 2 to 3 had particularly poor outcomes despite aggressive treatment. • These findings support the early use of the most effective therapies and provide a real-world benchmark for interpreting recent phase III trials. The treatment landscape for metastatic urothelial carcinoma (mUC) has rapidly evolved with immune checkpoint inhibitors (ICI), FGFR-targeted therapies, antibody-drug conjugates, and more recently first-line enfortumab vedotin (EV) plus pembrolizumab. In many countries, this combination is not yet available, and the standard of care (SOC) remains platinum-based chemotherapy (PBC) followed by ICI. Real-world data on treatment sequencing and attrition across therapy lines in unselected populations are limited. We analyzed patients with mUC treated between January 2020 and December 2023 across 4 French oncology centers. Eligible patients had received at least 1 cycle of PBC. Overall survival (OS), treatment sequences, and attrition rates were assessed. Survival was estimated using Kaplan–Meier methods. A total of 180 patients were included (median age 72 years; 81% male; 84% urothelial carcinoma). All received first-line PBC; 127 (71%) were non-progressive and eligible for avelumab maintenance, but 24 (19%) did not receive it. Only 54 patients (64%) received second-line therapy, and 45 (25%) reached third-line treatment. Median OS was 22.4 months (95% CI: 17.2–26.7). Patients receiving PBC followed by avelumab maintenance achieved a median OS of 29.0 months, compared with 15.6 months for not reponsders PBC patients. Patients with ECOG 2 to 3 ( n = 36) had poor outcomes (median OS 7.2 months vs. 26.4 months for ECOG 0–1; P < 0.001). This study confirms the real-world effectiveness of contemporary treatment sequences, highlights significant attrition between therapy lines, and underscores the need for upfront use of effective agents, particularly in patients with poor performans status.
Moinard-Butot et al. (Sat,) studied this question.