Sasanlimab + BCG Improves Event-Free Survival in High-Risk NMIBC: CREST Study Results - Neal Shore

Introduction

• Presenter: Neal Shore
• Interviewer: Sam Chang
• Event: AUA 2025 in Las Vegas
• Topic: CREST trial results on Sasanlimab + BCG for high-risk NMIBC

Study Overview

• Trial Name: CREST
• Phase: Phase 3
• Participants: 1000 patients
• Conditions: High-risk non-muscle invasive bladder cancer (NMIBC)
• Treatment Arms:
  • Sasanlimab + BCG
  • BCG alone
• Outcome: Successfully met endpoint of improved event-free survival (EFS) with combination therapy

Key Highlights

• Sasanlimab: A PD-1 checkpoint inhibitor delivered subcutaneously
• Advantages of Subcutaneous Delivery:
  • Quicker and easier than intravenous administration
  • Benefits clinic throughput
• Significance: Offers a new bladder-sparing option, potentially avoiding radical cystectomy
• Mechanism: BCG up-regulates PD expression, making PD blockers a logical combination partner

Side Effects

• General: Immune-related side effects typical for this class of drugs
• Specific Side Effects:
  • 16% Grade 3 or 4 events
  • Thyroid issues (typically hypothyroid)
  • Rash
  • Low single-digit percentages for elevated amylase or transaminase

Discussion and Insights

• Community Reception:
  • Urologic community may embrace due to subcutaneous delivery method
  • Urologists may need support from medical oncologists for managing immune-related adverse events
• Potential Impact: May lead to a paradigm shift in treatment options for NMIBC
• Future Directions:
  • Further exploration of antibody-drug conjugates
  • Emphasis on bladder-sparing treatments
  • Optimizing treatment stratification and synergy in mechanisms of action

Closing Remarks

• Overall Outlook: Positive development for bladder cancer treatment
• Next Steps: Awaiting publication, broader adoption in clinical practice likely pending further results
• Acknowledgment: Neal Shore's leadership and contributions to uro-oncology research