What question did this study set out to answer?

The study aims to evaluate the real-world efficacy and safety of immune checkpoint blockade in advanced urothelial carcinoma with histologic variants.

May 26, 2026Cancer Immunology Immunotherapy0 citationsOpen Access

Real-world efficacy and safety of immune checkpoint blockades in advanced urothelial carcinoma with histologic variant subtypes: the pembroblad study

KAKarim Amrane LCLuca Campedel FMFabien Moinard-Butot

Key Points

The study aims to evaluate the real-world efficacy and safety of immune checkpoint blockade in advanced urothelial carcinoma with histologic variants.
Retrospective analysis of patients receiving second-line anti-PD-(L)1 monotherapy after platinum failure.
Conducted across 24 centers in France from 2016 to 2022.
Primary endpoint focused on overall survival, with secondary endpoints on progression-free survival, objective response rate, and safety.
Median overall survival for UC-V was 8.5 months and for NUC was 10.5 months (95% CI, 3.5-22.8).
Median progression-free survival was 2.5 months for UC-V and 2.6 months for NUC.
Objective response rate was 31.4% overall, with 10.8% of patients experiencing grade ≥ 3 immune-related adverse events.

Abstract

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.

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