Standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT) is intravesical instillation with Bacillus Calmette-Guérin (BCG) (induction and maintenance regimens); however, BCG therapy still fails in 30 to 40% of patients.
Prior studies suggest that programmed death-ligand 1 (PD-L1) expression and alterations in immune infiltration might be associated with BCG failure.
The ALBAN trial is an international, 1:1 randomized, open-label phase 3 trial, comparing the combination of atezolizumab (an anti-PD-L1 antibody) and BCG (Arm B) versus BCG alone (Arm A) for BCG-naive patients with high-risk NMIBC. The primary endpoint was investigator-assessed event-free survival (EFS). Key secondary endpoints included high-grade recurrence-free survival (RFS), complete response (CR) rate and duration of response (DOR) in patients with carcinoma in situ (CIS) disease, as well as overall survival (OS).
In total, 255 patients were randomized in Arm A and 262 in Arm B. The trial did not meet its primary endpoint; there was no significant difference in EFS between both arms with a hazard ratio (HR) of 0.98 (95% confidence interval [CI]: 0.71-1.36); P = 0.9106. EFS results were consistent across all prespecified subgroups. The safety profile of the treatment combination was consistent with that of the individual agents but showed higher rates of treatment-related adverse events (TRAEs) and grade ≥3 TRAEs than BCG alone.
This phase 3 trial in BCG-naive patients with high-risk NMIBC did not demonstrate an EFS benefit from the addition of atezolizumab to 1-year BCG therapy in contrast to positive EFS results reported with another PD-(L)1 agent, suggesting that any benefit from checkpoint-BCG therapy may be context- and agent-specific rather than class effect. Future research should focus on biomarker-driven patient selection and optimization of the timing, duration, and route of checkpoint delivery relative to BCG.
Annals of oncology : official journal of the European Society for Medical Oncology. 2025 Dec 31 [Epub ahead of print]
M Roupret, A Bertaut, G Pignot, Y Neuzillet, N Houede, R Mathieu, L Corbel, D Besson, T Seisen, L Jaffrelot, C Lebacle, S Champiat, S Lebdai, M-O Timsit, C Thibault, L Goeman, Á Juárez Soto, C La, C Léger, Y Loriot
Sorbonne University, GRC 5 Predictive Onco-Uro, AP-HP, Urology, Pitie-Salpetriere Hospital, F-75013 Paris, France. Electronic address: ., Biostatistics, Centre Georges-François Leclerc (CGFL), Dijon, France., Surgical Oncology Department, IPC - Institut Paoli-Calmettes, Marseille, Cedex, France., Urology, Hôpital Foch, Paris-Saclay - UVSQ University, Suresnes, France., Department of Oncology, CHU Nîmes, Univ. Montpellier, Nîmes, France., Urology, CHU de Rennes - Hôpital Pontchaillou, Rennes, Cedex, France., Urology, Hôpital Privé des Côtes d'Armor, Plérin, France., Medical Oncology, Hôpital Privé des Côtes d'Armor, Plérin, France., Sorbonne University, GRC 5 Predictive Onco-Uro, AP-HP, Urology, Pitie-Salpetriere Hospital, F-75013 Paris, France., Sorbonne University, AP-HP, Medical oncology, Pitie-Salpetriere Hospital, F-75013 Paris, France., Urology, Hôpital Bicetre, Le Kremlin-Bicêtre, France., Drug Development Department (DITEP), Institut Gustave Roussy, Villejuif, Cedex, France., Urology, CHU Angers, Angers, France., Department of Urology, Georges-Pompidou European Hospital, AP-HP, Université Paris Cité, Paris, France., Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, AP-HP Centre, Université de Paris Cité, Paris, France., Urology, AZ Delta., Roeselare, Belgium., Urology, Hospitales Universitarios de Jerez de la Frontera y Punta de Europa, Spain., Research and Development, Unicancer, Paris, France., Gustave Roussy, Département de Médecine Oncologique et Département des Essais Précoces, Université Paris-Saclay, Villejuif, France.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41110692