Many real-world patients with advanced biliary tract cancer (BTC) are excluded by TOPAZ-1 criteria; this study assessed cisplatin and gemcitabine plus durvalumab (CGD) efficacy and safety in these patients. Data from 1358 patients with advanced BTC treated with first-line CGD across 55 international centers were retrospectively analyzed. Patients were classified as TOPAZ-1-in (meeting all inclusion criteria) or TOPAZ-1-out (meeting ≥ 1 exclusion criterion). Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Furthermore, OS and PFS of the TOPAZ-1-out cohort were compared with reconstructed survival data from the phase III trial. 912 (67.1%) patients were classified as TOPAZ-1-in, and 446 (32.9%) as TOPAZ-1-out. After a median follow-up of 14.5 months (95% CI: 13.7–36.5), OS was 16.1 months in TOPAZ-1-in and 12.5 months in TOPAZ-1-out (HR 0.69, 95% CI: 14.6–16.5, p = 0.0001); PFS was 8.2 versus 6.5 months (HR 0.73, 95% CI: 7.1–8.1, p < 0.0001). Median OS in the TOPAZ-1-out cohort (12.5 months) was nearly identical to the phase III trial experimental arm (12.9 months; HR 1.15, p = 0.13); for PFS the HR was 1.12 (95% CI 0.93–1.42; p = 0.09). Among TOPAZ-1-out patients, active infection, elevated bilirubin, and ECOG PS > 1 were linked to poorer OS, while no detrimental impact emerged for ALT/AST abnormalities, corticosteroid use, renal or hematologic parameters, or prior surgery within 6 months, suggesting treatment effectiveness was broadly maintained across clinical subgroups. Furthermore, TOPAZ-1-out patients experienced no significant increase in adverse events compared with the TOPAZ-1-in group. Real-world data suggest CGD may be effective in TOPAZ-1-out patients, with no evident increase in toxicity, supporting the potential expanded use of the regimen in clinical practice.
Outcomes of Cisplatin, Gemcitabine, and Durvalumab According to TOPAZ-1 Study Eligibility: A Large Global Analysis in a Real-World Setting
Ghidini M.;
2026-01-01
Abstract
Many real-world patients with advanced biliary tract cancer (BTC) are excluded by TOPAZ-1 criteria; this study assessed cisplatin and gemcitabine plus durvalumab (CGD) efficacy and safety in these patients. Data from 1358 patients with advanced BTC treated with first-line CGD across 55 international centers were retrospectively analyzed. Patients were classified as TOPAZ-1-in (meeting all inclusion criteria) or TOPAZ-1-out (meeting ≥ 1 exclusion criterion). Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Furthermore, OS and PFS of the TOPAZ-1-out cohort were compared with reconstructed survival data from the phase III trial. 912 (67.1%) patients were classified as TOPAZ-1-in, and 446 (32.9%) as TOPAZ-1-out. After a median follow-up of 14.5 months (95% CI: 13.7–36.5), OS was 16.1 months in TOPAZ-1-in and 12.5 months in TOPAZ-1-out (HR 0.69, 95% CI: 14.6–16.5, p = 0.0001); PFS was 8.2 versus 6.5 months (HR 0.73, 95% CI: 7.1–8.1, p < 0.0001). Median OS in the TOPAZ-1-out cohort (12.5 months) was nearly identical to the phase III trial experimental arm (12.9 months; HR 1.15, p = 0.13); for PFS the HR was 1.12 (95% CI 0.93–1.42; p = 0.09). Among TOPAZ-1-out patients, active infection, elevated bilirubin, and ECOG PS > 1 were linked to poorer OS, while no detrimental impact emerged for ALT/AST abnormalities, corticosteroid use, renal or hematologic parameters, or prior surgery within 6 months, suggesting treatment effectiveness was broadly maintained across clinical subgroups. Furthermore, TOPAZ-1-out patients experienced no significant increase in adverse events compared with the TOPAZ-1-in group. Real-world data suggest CGD may be effective in TOPAZ-1-out patients, with no evident increase in toxicity, supporting the potential expanded use of the regimen in clinical practice.
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