What is the role of durvalumab (Imfinzi) in the treatment of a fit patient with T3N0 urinary bladder cancer, specifically in the context of the Niagra regime?

Durvalumab in the NIAGARA Regimen for Muscle-Invasive Bladder Cancer

For fit patients with T3N0 muscle-invasive bladder cancer, perioperative durvalumab added to neoadjuvant gemcitabine-cisplatin chemotherapy followed by radical cystectomy represents the new standard of care, demonstrating superior event-free survival (67.8% vs 59.8% at 2 years) and overall survival (82.2% vs 75.2% at 2 years) compared to chemotherapy alone. 1, 2, 3

NIAGARA Trial Results

The landmark NIAGARA phase 3 randomized trial enrolled 1,063 cisplatin-eligible patients with muscle-invasive bladder cancer (cT2-4a N0M0) and demonstrated:

• Event-free survival benefit: Hazard ratio 0.68 (95% CI 0.56-0.82; p<0.001) with durvalumab versus chemotherapy alone 1, 3
• Overall survival benefit: Hazard ratio 0.75 (95% CI 0.59-0.93; p=0.01) at median follow-up of 42.3 months 1, 3
• High surgical completion rate: 88.0% of patients in the durvalumab group underwent radical cystectomy versus 83.2% in the chemotherapy-alone group 3

Treatment Protocol

The NIAGARA regimen consists of three phases:

Neoadjuvant Phase:

• Durvalumab 1500 mg IV plus gemcitabine-cisplatin every 3 weeks for 4 cycles 3
• Gemcitabine and cisplatin dosed per standard protocols 1

Surgical Phase:

• Radical cystectomy with bilateral pelvic lymph node dissection (including common iliac, internal iliac, external iliac, and obturator nodes) 1
• Surgery should not be delayed; median time to cystectomy in NIAGARA was appropriate 2

Adjuvant Phase:

• Durvalumab 1500 mg IV every 4 weeks for 8 cycles (approximately 8 months) 3

Safety Profile

The addition of durvalumab did not increase treatment-related toxicity:

• Grade 3-4 treatment-related adverse events: 40.6% with durvalumab versus 40.9% with chemotherapy alone 3
• Treatment-related deaths: 0.6% in both groups 3
• Common immune-related adverse events requiring monitoring: Endocrinopathies, hepatitis, colitis, nephritis 2

Clinical Context and Guideline Recommendations

The European Association of Urology (2025) now recommends perioperative durvalumab with neoadjuvant gemcitabine-cisplatin as the standard of care for cisplatin-eligible muscle-invasive bladder cancer. 1, 2 This represents a paradigm shift from the previous standard of neoadjuvant chemotherapy alone, which provided only a 5% absolute survival benefit at 5 years. 2

For your T3N0 patient specifically:

• T3 disease qualifies as muscle-invasive bladder cancer requiring neoadjuvant therapy 1
• Node-negative status (N0) does not exclude benefit from the NIAGARA regimen 3
• "Fit" status suggests cisplatin eligibility, making this patient ideal for the full NIAGARA protocol 1, 2

Important Caveats

Regulatory approval is pending for this regimen despite the compelling trial data and guideline recommendations. 1 However, the strength of evidence and guideline endorsement support its use in appropriate clinical settings.

Do not substitute durvalumab in other settings without evidence: Durvalumab failed to meet primary endpoints in the DANUBE trial for first-line metastatic disease 1, 4, and lacks supporting evidence for adjuvant use post-cystectomy (where nivolumab is the evidence-based choice). 5

PD-L1 testing is not required: The NIAGARA trial did not stratify by PD-L1 status, and benefit was observed across the study population. 3 This contrasts with durvalumab's use in metastatic disease, where PD-L1 expression was more predictive. 1

Comparison to Historical Standards

The NIAGARA results substantially exceed the modest benefits previously seen with neoadjuvant chemotherapy alone, which meta-analyses showed provided only a 5% absolute survival benefit at 5 years. 2 The 7.4% absolute improvement in 2-year event-free survival and 7.0% improvement in overall survival represent clinically meaningful advances. 3