Durvalumab–Gemcitabine–Cisplatin (TOPAZ-1) Remains Effective in Real-World Biliary Tract Cancer: IJC | August 2026

Introduction:

Durvalumab plus gemcitabine–cisplatin (CGD) is standard first-line therapy for advanced biliary tract cancer (BTC) based on TOPAZ-1. However, clinical trials exclude many patients encountered in everyday practice. This large global study evaluated whether CGD remains effective and safe in patients who would not have met TOPAZ-1 eligibility criteria.

Why was this study needed?

Trial populations are often fitter and more selected than real-world patients.

Nearly one-third of patients receiving CGD may fall outside TOPAZ-1 eligibility criteria.

Clinicians need evidence on whether trial exclusions should limit use of CGD in routine practice.

Identifying specific high-risk features may improve patient selection.

Results:

Among 1,358 patients across 55 international centers, one-third would have been excluded from TOPAZ-1.

TOPAZ-1-in patients had better survival, but TOPAZ-1-out patients still achieved a median OS of 12.5 months, remarkably similar to the 12.9 months reported with CGD in TOPAZ-1.

Active infection, elevated bilirubin, and ECOG >1 identified poorer outcomes, whereas several other trial-exclusion factors did not appear to compromise effectiveness.

Importantly, broader real-world eligibility was not associated with increased overall toxicity.

Clinical Impact:

These findings suggest that TOPAZ-1 eligibility criteria should not automatically define who can receive durvalumab–gemcitabine–cisplatin in clinical practice. Carefully selected patients outside traditional trial criteria may still derive meaningful benefit, although infection, hyperbilirubinemia, and poor performance status warrant particular caution.

Bottom Line:

Durvalumab plus gemcitabine–cisplatin remains effective and tolerable in many advanced BTC patients who would have been excluded from TOPAZ-1. Real-world treatment decisions should therefore be individualised rather than based solely on original trial eligibility criteria.