Phase 3 ALBAN Trial Shows Atezolizumab Plus BCG Fails to Improve Outcomes in High-Risk Bladder Cancer
Key Insights
The phase 3 ALBAN trial demonstrated that adding atezolizumab (Tecentriq) to standard BCG therapy did not significantly improve event-free survival in BCG-naive patients with high-risk non-muscle-invasive bladder cancer.
The combination therapy showed no benefit for the primary endpoint with 73 events in 262 patients receiving atezolizumab plus BCG versus 72 events in 255 patients receiving BCG alone.
Safety analysis revealed higher rates of treatment-related adverse events in the combination arm, with 94% experiencing any-grade side effects compared to 76% in the BCG-only group.
The addition of atezolizumab (Tecentriq) to standard Bacillus Calmette-Guérin (search) (BCG) therapy failed to improve outcomes in patients with high-risk, non-muscle-invasive bladder cancer (NMIBC), according to results from the phase 3 ALBAN trial presented at the 2025 European Society for Medical Oncology (search) (ESMO (search)) Congress and simultaneously published in the Annals of Oncology.
The study showed no significant improvement in the primary endpoint of event-free survival (EFS) with the combination therapy compared to BCG alone (HR, 0.98; 95% CI, 0.71–1.36; P = 0.9106) in BCG-naive patients with high-risk NMIBC.
Trial Results Show No Clinical Benefit
The ALBAN study reported 73 events among 262 patients in the experimental combination arm versus 72 events among 255 patients receiving BCG alone. Events were defined as high-grade or low-grade NMIBC relapse, persistence of carcinoma in situ (CIS) after 6 months, progression of disease, appearance of upper tract urothelial carcinoma, or death from any cause.
"You don't have to be a statistician to see the [Kaplan-Meier] curves are very close to one another," said Dr. Morgan Roupret, professor of urology at Sorbonne University (search) in Paris, France, who presented the findings.
The secondary endpoint of high-grade recurrence-free survival (RFS), defined as reappearance of high-grade NMIBC or death from any cause, also showed no improvement in the experimental arm (HR, 1.06; 95% CI, 0.73–1.55; P = 0.7658). While overall survival data were not yet mature for analysis, there was no impact on median survival with the addition of atezolizumab (HR, 1.73; 95% CI, 0.73–3.92; P = 0.1799).
Safety Profile Reveals Increased Toxicity
The combination therapy demonstrated a notably higher toxicity profile compared to BCG monotherapy. Any-grade treatment-related adverse events occurred in 94% (240 patients) of those receiving the combination versus 76% (189 patients) in the control arm.
Grade 3 or higher treatment-related adverse events occurred in 23% (58 patients) of the atezolizumab combination group compared to 9% (22 patients) in the BCG-only group. Serious treatment-related adverse events were reported in 24% (60 patients) and 8% (21 patients) of patients, respectively.
Treatment discontinuation due to adverse events was substantially higher in the experimental arm, occurring in 29% (73 patients) versus 9% (22 patients) in the control group. Dose interruptions due to side effects affected 18% (47 patients) in the combination arm compared to 8% (9 patients) receiving BCG alone.
In the experimental arm, 13% (32 patients) withdrew from BCG only, 16% (41 patients) withdrew from atezolizumab only, and 3% (8 patients) withdrew from both treatments.
"Side effects such as rash and pruritus were common and consistent with previously published data. There was no particular surprise," Roupret noted during the presentation.
Study Design and Patient Population
The ALBAN study enrolled 517 BCG-naive patients with high-risk NMIBC following first- and second-look transurethral resection of bladder tumor (TURBT). High-risk disease was defined as the presence of any high-grade or grade 3 Ta or T1 tumors and/or carcinoma in situ. Patients were required to have no metastatic disease in the pelvis, abdomen, or chest and an ECOG performance status of 0 to 2.
Participants were randomized 1:1 to receive BCG once weekly for 6 weeks during induction, followed by maintenance therapy once weekly for 3 weeks at 3, 6, and 12 months, with or without atezolizumab administered at 1200 mg intravenously every 3 weeks for up to 1 year.
Patient characteristics were well-balanced between treatment arms. The median age was 68 years in the combination arm versus 67 years in the control arm. Male patients comprised 84% (221 patients) of the experimental arm and 87% (221 patients) of the control arm.
The only notable difference between arms was smoking history, with 66% (173 patients) identified as former smokers and 19% (50 patients) as current smokers in the experimental arm, compared to 62% (157 patients) former smokers and 15% (38 patients) current smokers in the control arm.
Future Research Directions
Roupret concluded that future research will focus on biomarker-driven patient selection based on integrated molecular and spatial immune profiling. He emphasized the need to optimize the timing, duration, and delivery route of checkpoint inhibitors in NMIBC treatment.
The negative results from ALBAN represent a setback for combination immunotherapy approaches in high-risk NMIBC, highlighting the complexity of enhancing BCG's established efficacy in this patient population.