What dose of durvalumab (generic name) do NICE guidelines suggest for a fit patient with T3N0 urinary bladder cancer undergoing the Niagra regime?

Durvalumab Dosing in the NIAGARA Regimen for T3N0 Bladder Cancer

NICE guidelines do not specifically address the NIAGARA regimen, as this is a recently approved perioperative protocol; however, the European Association of Urology 2025 guidelines describe the NIAGARA trial dosing as durvalumab 1500 mg every 4 weeks administered with neoadjuvant cisplatin/gemcitabine chemotherapy followed by radical cystectomy and continued as maintenance therapy. 1

NIAGARA Regimen Dosing Protocol

The standard NIAGARA protocol uses durvalumab 1500 mg intravenously every 4 weeks, which has demonstrated significant survival benefits in the phase 3 trial. 1, 2

Neoadjuvant Phase

• Administer durvalumab 1500 mg IV every 3 weeks for four cycles concurrently with gemcitabine-cisplatin chemotherapy 2
• This perioperative addition to neoadjuvant chemotherapy significantly improved event-free survival (67.8% vs 59.8% at 24 months; HR 0.68; p<0.001) 1, 2
• Overall survival at 24 months was 82.2% with durvalumab versus 75.2% without (HR 0.75; p=0.01) 1, 2

Surgical Phase

• Perform radical cystectomy after completing neoadjuvant therapy 1, 2
• In the NIAGARA trial, 88.0% of patients in the durvalumab group successfully underwent radical cystectomy 2

Adjuvant Maintenance Phase

• Continue durvalumab 1500 mg IV every 4 weeks for eight cycles following radical cystectomy 2
• This maintenance dosing is critical for achieving the demonstrated survival benefits 1

Pharmacokinetic Rationale for Fixed Dosing

The 1500 mg every 4 weeks fixed dose is supported by pharmacokinetic data showing no meaningful relationship between dose, drug exposure, or adverse event rates across the evaluated range of 0.1 to 10 mg/kg Q2W, 15 mg/kg Q3W, and 20 mg/kg Q4W. 1

• PK simulations demonstrated that 10 mg/kg Q2W maintains >99% target saturation, and flat dosing of 1500 mg Q4W achieves comparable exposure 1
• No dose-limiting toxicities were identified in dose-finding studies 1

Safety Profile in NIAGARA

Treatment-related adverse events of grade 3 or 4 occurred in 40.6% of patients receiving durvalumab plus chemotherapy versus 40.9% with chemotherapy alone, demonstrating that adding durvalumab does not substantially increase toxicity. 2

• Treatment-related deaths occurred in only 0.6% of patients in each group 2
• The regimen was well-tolerated with manageable toxicity 2

Critical Clinical Considerations

For your fit patient with T3N0 bladder cancer, the NIAGARA regimen represents the most recent high-quality evidence for perioperative immunotherapy, though regulatory approval is still pending in many jurisdictions. 1

• The trial included patients with cT2-4a N0M0 disease, making your T3N0 patient an appropriate candidate 1
• Cisplatin eligibility is required for this protocol 1, 2
• The significant improvements in both event-free survival and overall survival support this approach over chemotherapy alone 1, 2

Alternative Dosing in Other Settings

While the NIAGARA protocol uses 1500 mg Q4W, other durvalumab studies in metastatic urothelial carcinoma have used 10 mg/kg Q2W or 1500 mg Q4W with similar efficacy. 1, 3, 4

• In the STRONG study, fixed-dose durvalumab 1500 mg Q4W demonstrated acceptable safety and durable clinical activity in previously treated patients 3
• The median overall survival was 18.2 months with 1500 mg Q4W dosing in platinum-refractory disease 4

However, for the specific NIAGARA perioperative protocol in muscle-invasive bladder cancer, the evidence-based dose is durvalumab 1500 mg IV every 4 weeks (every 3 weeks during neoadjuvant phase, every 4 weeks during maintenance). 1, 2