Real-world data from patients with advanced biliary tract cancer (BTC) treated with first-line durvalumab plus cisplatin and gemcitabine across 12 countries/regions show similar survival outcomes between those who would not be eligible for the TOPAZ-1 trial and results reported in the durvalumab arm of TOPAZ-1, with no evident increase in toxicity.
“While these findings should be interpreted with caution, they support the potential use of durvalumab plus cisplatin and gemcitabine in selected patients in routine clinical practice, provided that careful patient selection and close monitoring are adopted,” the researchers suggested. [Int J Cancer 2026;doi:10.1002/ijc.70699]
The pivotal phase III TOPAZ-1 trial excluded patients with relapse ≤6 months after surgery, Eastern Cooperative Oncology Group (ECOG) performance status (PS) >1, use of corticosteroids at doses >10 mg daily, or clinically relevant parameters indicative of inadequate organ or marrow function. “These strict criteria excluded a significant proportion of patients commonly encountered in clinical practice, limiting the applicability of the new therapeutic strategy in real-world settings,” the researchers noted.
They therefore retrospectively analyzed efficacy outcomes and safety in a real-world setting in 1,358 patients with advanced BTC treated with first-line durvalumab plus cisplatin and gemcitabine across 55 centres in 12 countries/regions (Austria, Belgium, China, Germany, Hong Kong, Italy, Korea, Portugal, Spain, UK, and US) between March 2022 and April 2025.
The cohort included 912 patients (67.1 percent) who met all inclusion criteria of TOPAZ-1 (TOPAZ-1-in group; male, 50.3 percent; median age, 69 years; metastatic disease, 80.3 percent), and 446 patients (32.9 percent) who presented with ≥1 TOPAZ-1 exclusion criteria (TOPAZ-1-out group; male, 56.5 percent; median age, 69 years). The two groups differed significantly in terms of gender (p=0.03), primary tumour site (p<0.002), and presence of biliary drainage or stent (21.3 vs 54.7 percent; p<0.0001). The most common TOPAZ-1 exclusion characteristics were early recurrent disease and liver function abnormalities.
Similar survival outcomes in TOPAZ-1-out patients
After a median follow-up of 14.5 months, median overall survival (OS) was 16.1 months in the TOPAZ-1-in group compared with 12.5 months in the TOPAZ-1-out group (hazard ratio [HR], 0.69; 95 percent confidence interval [CI], 0.69–0.83; p=0.0001). Median progression-free survival (PFS) was 8.2 vs 6.5 months (HR, 0.73; 95 percent CI, 0.63–0.85; p<0.0001).
“Median OS in the TOPAZ-1-out cohort was nearly identical to that in the phase III trial’s experimental arm [12.9 months; HR, 1.15; p=0.13],” the researchers highlighted.
“At all predefined time points up to 30 months, survival probabilities were nearly superimposable [between the TOPAZ-1-out cohort and the durvalumab arm of the TOPAZ-1 trial],” they added. “At 6, 12, 18, 24 and 30 months, OS probabilities in the TOPAZ-1-out cohort were 77, 52, 40, 28 and 22 percent, respectively, compared with 74, 56, 42, 31 and 20 percent in the trial [all p>0.20].”
Median PFS in the TOPAZ-1-out cohort was also comparable to that reported in TOPAZ-1’s durvalumab arm (7.2 months) (HR, 1.12; 95 percent 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 alanine aminotransferase or aspartate aminotransferase abnormalities, corticosteroid use, renal or haematologic parameters, or prior surgery within 6 months, suggesting that treatment effectiveness was broadly maintained across clinical subgroups,” the researchers noted.
Active infection and ECOG PS >1 were also significantly associated with poorer PFS in TOPAZ-1-out patients.
Of note, TOPAZ-1-out patients experienced no significant increase in adverse events compared with the TOPAZ-1-in cohort.
“Overall, these findings suggest that several exclusion parameters might have no clinical impact on outcomes and safety, supporting a more flexible interpretation of eligibility criteria in real-world clinical practice,” the researchers suggested.