What is the recommended duration and number of cycles of durvalumab for a patient with ypT2aN1 urothelial carcinoma of the bladder, post radical cystectomy?

Adjuvant Durvalumab for ypT2aN1 Urothelial Carcinoma Post-Cystectomy

For ypT2aN1 urothelial carcinoma of the bladder post radical cystectomy, adjuvant nivolumab (not durvalumab) is the evidence-based recommendation, administered at 240 mg IV every 2 weeks (or 480 mg IV every 4 weeks) for up to 1 year. 1

Critical Distinction: Nivolumab vs Durvalumab

• Nivolumab is the only checkpoint inhibitor with FDA approval and Level A evidence for adjuvant treatment in high-risk urothelial carcinoma post-cystectomy, based on the CheckMate274 trial which demonstrated significantly improved disease-free survival in patients with ypT2-ypT4 or node-positive disease after neoadjuvant chemotherapy 1

• Durvalumab does not have established evidence or approval for the adjuvant post-cystectomy setting in urothelial carcinoma 1, 2

• The AMBASSADOR trial using adjuvant pembrolizumab has reported meeting its endpoint for improved disease-free survival, but full results are still pending 1

Specific Treatment Protocol for Your Patient

Eligibility Confirmation

• Your patient with ypT2aN1 disease (node-positive after neoadjuvant chemotherapy) meets high-risk criteria for adjuvant immunotherapy 1
• Node-positive disease carries approximately 70% systemic recurrence risk without additional treatment 1

Recommended Regimen: Adjuvant Nivolumab

• Dose: Nivolumab 240 mg IV every 2 weeks OR 480 mg IV every 4 weeks 1
• Duration: Continue for 1 year (up to 52 weeks) 1
• Timing: Initiate within 90 days of cystectomy for maximum benefit, though some benefit persists even after 90 days 1

Why Durvalumab Is Not Appropriate Here

• Durvalumab's evidence base in urothelial carcinoma is limited to:

  • Metastatic/locally advanced disease after platinum-based chemotherapy (10 mg/kg IV every 2 weeks or 1500 mg IV every 4 weeks) 2, 3
  • First-line metastatic disease (where it failed to meet primary endpoints in the DANUBE trial) 4
  • Concurrent with radiation therapy in localized disease (investigational) 5

• No published data support durvalumab in the adjuvant post-cystectomy setting 1, 2, 4

Alternative if Nivolumab Unavailable

• If nivolumab is not accessible, consider:
  • Adjuvant cisplatin-based chemotherapy (gemcitabine-cisplatin or dose-dense MVAC) for minimum 3 cycles, though your patient already received neoadjuvant chemotherapy 1
  • Close surveillance without additional systemic therapy, recognizing the high recurrence risk 1

Common Pitfalls to Avoid

• Do not substitute durvalumab for nivolumab in the adjuvant setting—they are not interchangeable, and durvalumab lacks supporting evidence for this indication 1, 2

• Do not delay treatment initiation beyond 90 days post-cystectomy, as retrospective analysis shows greatest benefit when started within this window 1

• Do not omit adjuvant therapy in node-positive disease—the 70% recurrence risk mandates systemic treatment 1

• Do not use atezolizumab as an alternative, as the IMvigor010 trial failed to demonstrate statistically significant improvement in this setting 1

Monitoring During Treatment

• Grade 3-4 treatment-related adverse events occur in approximately 14-27% of patients receiving checkpoint inhibitors 2, 4
• Monitor for immune-mediated adverse events including hepatitis, pneumonitis, colitis, endocrinopathies, and nephritis 2, 3
• Most recurrences occur within the first 2-3 years after cystectomy, necessitating close surveillance 1