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.
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.
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 10.5[95% 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.
Anti-PD-(L)1 monotherapy shows clinical benefit in advanced UC-V and NUC after platinum failure.
Cancer immunology, immunotherapy : CII. 2026 May 24 [Epub ahead of print]
Karim Amrane, Luca Campedel, Fabien Moinard-Butot, Mathilde Gout, Hakim Mahammedi, Mostefa Bennamoun, Tressie Herrmann, Pierre-Etienne Gabriel, Damien Pouessel, Matthieu Roulleaux-Dugage, Constance Thibault, Mathilde Cancel, Aude Flechon, Olivier Huillard, Baptiste Abbar, Delphine Borchiellini, Louis Doublet, Laëtitia Augusto-Pelegrin, Elouen Boughalem, Pierre Cornillon, Clément Dumont, Philippe Barthélémy
Département d'Innovation Thérapeutique Et Des Essais Précoces (DITEP), Institut Gustave Roussy, Université Paris Saclay, Villejuif, France. ., Department of Medical Oncology, Saint-Etienne University Hospital Center, Saint-Priest-en-Jarez, France., Department of Medical Oncology, University Hospital Strasbourg, Strasbourg, France., Department of Medical Oncology Jean Perrin Cancer Center, Clermont-Ferrand, France., Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France., Department of Medical Oncology, Saint-Louis Hospital, AP-HP, Paris Cité University, Paris, France., Univ Toulouse, Oncopole Claudius Regaud, IUCT-Oncopole, Toulouse, France., Department of Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP.Centre, Université Paris Cité, Paris, France., Department of Medical Oncology, Centre Hospitalier Universitaire, Tours, France., Léon Bérard Cancer Center, Department of Medical Oncology, Lyon, France., Department of Medical Oncology, Cochin University Hospital, Université Paris Cité, Institut du Cancer Paris CARPEM, Paris, France., Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France., Department of Medical Oncology, Antoine Lacassagne Cancer Center, Nice, France., Hôpital Privé Drôme-Ardèche, Valence, France., Department of Medical Oncology, Rouen University Hospital, Rouen, France., Oncology Department, Institut de Cancérologie de L'Ouest, Angers, France.