Does the National Institute for Health and Care Excellence (NICE) suggest the use of durvalumab (durvalumab) in a fit patient with T3N0 urinary bladder cancer?

NICE Guidelines on Durvalumab for Bladder Cancer

NICE (National Institute for Health and Care Excellence) guidelines are not represented in the provided evidence, and no NICE-specific recommendations for durvalumab in bladder cancer are available in these sources. However, multiple international guidelines and high-quality evidence address durvalumab's role in bladder cancer treatment.

Current Guideline-Based Recommendations for Durvalumab

Perioperative Setting (Muscle-Invasive Disease)

For a fit patient with T3N0 bladder cancer, durvalumab combined with neoadjuvant gemcitabine-cisplatin followed by radical cystectomy represents the new standard of care based on the NIAGARA trial. 1

• The European Association of Urology recommends this perioperative durvalumab regimen as standard treatment for cisplatin-eligible muscle-invasive bladder cancer 1
• The NIAGARA trial demonstrated 2-year event-free survival of 67.8% with durvalumab versus 59.8% without (HR 0.68; p<0.001) 1, 2
• Overall survival at 2 years was 82.2% with durvalumab versus 75.2% without (HR 0.75; p=0.01) 1, 2
• The American Society of Clinical Oncology acknowledges these significant survival improvements 1
• NCCN guidelines indicate approval is pending following these results 1

Second-Line Metastatic Setting

Durvalumab is FDA-approved and recommended for locally advanced or metastatic urothelial carcinoma after platinum-based chemotherapy failure, but with lower evidence quality (category 2) compared to pembrolizumab (category 1). 3, 4

• The Society for Immunotherapy of Cancer consensus statement recommends durvalumab for patients previously treated with platinum-based chemotherapy or who relapsed within 12 months of perioperative platinum therapy 3
• NCCN guidelines from 2016-2017 included durvalumab as a second-line option alongside other checkpoint inhibitors 3
• Durvalumab showed increased antitumor activity in patients with high PD-L1 expression (≥25% staining in tumor or immune cells) 3

First-Line Metastatic Setting

Durvalumab is NOT recommended as first-line therapy for metastatic disease based on the failed DANUBE trial. 3, 5

• The DANUBE trial evaluating durvalumab with or without tremelimumab as first-line treatment did not meet either primary endpoint 3, 5
• Median overall survival was 14.4 months with durvalumab monotherapy versus 12.1 months with chemotherapy in high PD-L1 patients (HR 0.89; p=0.30) 5
• Durvalumab plus tremelimumab showed 15.1 months versus 12.1 months with chemotherapy (HR 0.85; p=0.075) 5

Clinical Application for T3N0 Disease

For your specific patient with T3N0 bladder cancer who is fit, the evidence-based approach is:

1. Administer neoadjuvant gemcitabine-cisplatin for 4 cycles (every 3 weeks) combined with durvalumab (1500 mg IV every 4 weeks) 1, 2

2. Proceed to radical cystectomy with bilateral pelvic lymph node dissection 1, 2

3. Continue adjuvant durvalumab (1500 mg IV every 4 weeks) for 8 additional cycles 1, 2

4. Monitor for immune-related adverse events, particularly endocrinopathies, hepatitis, and colitis 1

Important Caveats

• PD-L1 testing is not required for perioperative durvalumab decisions, as benefit was seen regardless of PD-L1 status in NIAGARA 1
• Treatment-related grade 3-4 adverse events occurred in 40.6% with durvalumab versus 40.9% with chemotherapy alone, showing comparable safety 2
• 88% of patients in the durvalumab arm completed radical cystectomy versus 83.2% in the chemotherapy-only arm 2
• Scotland specifically noted that additional cost-benefit evidence is required to justify immunotherapy agents 3

Alternative Scenarios

If the patient were cisplatin-ineligible: Standard neoadjuvant chemotherapy followed by cystectomy would be recommended, as durvalumab perioperative treatment is specifically for cisplatin-eligible patients 1

If disease were metastatic at presentation: Enfortumab vedotin plus pembrolizumab would be preferred first-line therapy, not durvalumab 6