BACKGROUND: Histologic variants (HV) of urothelial carcinoma (UC-V) and non-urothelial carcinomas (NUC) of the bladder and urinary tract are aggressive malignancies with poor prognosis and limited response to platinum-based chemotherapy. Despite their biological particularities and distinct immune microenvironments, these HV subtypes are under-represented in immune checkpoint blockade (ICB) trials. METHODS: PEMBROBLAD is a French national multicenter retrospective study conducted across 24 centers. We included patients with advanced UC-V or NUC who received second-line anti-PD-(L)1 monotherapy after progression on platinum-based chemotherapy between 2016 and 2022. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. RESULTS: We included 129 UC-V and 34 NUC. With a median follow-up was 21.9 months, the median OS was 8.6 95% confidence interval (CI), 5.3-11.2 months, with 8.5 95% CI 5.3-10.9 months for UC-V and 10.595% CI 3.5-22.8 months for NUC. The median PFS was 2.6 95% CI 2.1-3.4 months with 2.5 95% CI 2.0-3.4 months for the UC-V group and 2.6 2.0-3.4 months for the NUC group. ORR was 31.4% overall (complete response 15.3%, partial response 16.1%). In multivariable analysis, ECOG performance status ≥ 2 was independently associated with both poorer OS (HR 3.30, 95% CI 1.22-8.92; p = 0.018) and PFS (HR 2.32, 95% CI 1.52-3.54; p < 0.001). Pembrolizumab treatment was associated with improved PFS (HR 0.53, 95% CI 0.31-0.81; p = 0.017). Grade ≥ 3 immune-related adverse events occurred in 10.8% of patients, with no treatment-related deaths. CONCLUSIONS: Anti-PD-(L)1 monotherapy shows clinical benefit in advanced UC-V and NUC after platinum failure.
Amrane et al. (2026) studied this question.