Background
Phase III, open-label, randomized trial. N=1,018 patients with BCG-naive, high-risk non-muscle-invasive bladder cancer (NMIBC) after TURBT. Evaluated adding the PD-L1 inhibitor durvalumab to BCG induction and maintenance vs BCG alone. First successful immunotherapy + BCG combination in NMIBC; final analysis presented at ESMO 2025.
Interventions and follow up
Arm A: Durvalumab + BCG induction and maintenance (1 year durvalumab)
Arm B: BCG induction and maintenance alone
Primary endpoint: Disease-free survival (DFS) in the intent-to-treat population
Median follow up: 60.7 months (range 51.5–66.5 months)
Arm B: BCG induction and maintenance alone
Primary endpoint: Disease-free survival (DFS) in the intent-to-treat population
Median follow up: 60.7 months (range 51.5–66.5 months)
Results
Disease-free survival: HR 0.68 (95% CI 0.50–0.93), P=.015 — 32% reduction in recurrence/death; events 20% (67/336) vs 29% (98/340)
12-month DFS: 92% (durvalumab + BCG) vs 87% (BCG alone)
24-month DFS: 87% vs 82%
Overall survival: No significant detriment (HR 0.80, 95% CI 0.53–1.20); median OS not reached in either arm
12-month DFS: 92% (durvalumab + BCG) vs 87% (BCG alone)
24-month DFS: 87% vs 82%
Overall survival: No significant detriment (HR 0.80, 95% CI 0.53–1.20); median OS not reached in either arm
Adverse events
Grade 3–4 treatment-related AE: 21% (durvalumab + BCG) vs 4% (BCG alone)
Deaths: No treatment-related deaths; most toxicities attributable to the individual agents
Deaths: No treatment-related deaths; most toxicities attributable to the individual agents
Conclusions
Durvalumab added to BCG induction and maintenance significantly improved disease-free survival in BCG-naive high-risk NMIBC, a 32% reduction in recurrence or death, with manageable toxicity and no OS detriment. This is the first positive immunotherapy + BCG combination in NMIBC.
Key Limitations
Open-label design may introduce bias. Treatment completion was modest (~47% completed the full year of durvalumab + BCG), limiting interpretation of long-term adherence. OS data remain immature with medians not reached.
Clinical Context
POTOMAC is the first positive immunotherapy + BCG combination for NMIBC, supporting a potential new standard of 1 year of durvalumab with BCG for treatment-naive high-risk patients. It complements emerging intravesical and systemic options and may offer an alternative to early cystectomy. Incorporation into ESMO and EAU guidance awaits regulatory review and mature OS data.