# Durvalumab-Based First-Line Chemoimmunotherapy in Advanced Biliary Tract Cancer: Real-World Outcomes and Prognostic Factors—A Turkish Oncology Group Study

## TL;DR

This study confirms that combining durvalumab with chemotherapy is effective and safe for advanced biliary tract cancer in real-world settings, with patient health and liver function affecting outcomes.

## Contribution

The study provides real-world evidence of durvalumab-based chemoimmunotherapy effectiveness and identifies prognostic factors in advanced biliary tract cancer.

## Key findings

- Durvalumab plus chemotherapy showed meaningful clinical benefit with acceptable safety in advanced biliary tract cancer.
- Better performance status and preserved liver function were linked to longer survival.
- Immune-related side effects and tumor response were associated with improved outcomes.

## Abstract

Biliary tract cancers are aggressive malignancies that are frequently diagnosed at an advanced stage, limiting curative treatment options. The addition of durvalumab to standard chemotherapy has recently improved first-line treatment outcomes, but real-world data remain limited. In this multicenter national study from Türkiye, we evaluated the effectiveness and safety of durvalumab combined with chemotherapy in routine clinical practice and investigated factors associated with survival. We observed that this combination provided meaningful clinical benefit with an acceptable safety profile. Patients with better performance status and preserved liver function experienced longer survival. Moreover, the development of immune-related side effects and radiological tumor response were associated with improved outcomes. These findings offer real-world confirmation of the clinical value of durvalumab-based treatment and may contribute to more accurate patient selection in advanced biliary tract cancer.

Background: Durvalumab combined with gemcitabine–cisplatin (GC) has become the standard first-line treatment for advanced biliary tract cancer (BTC) following the TOPAZ-1 trial. However, real-world effectiveness, safety, and prognostic determinants, particularly in underrepresented populations, remain insufficiently defined. The aim of this study was to evaluate the real-world outcomes of first-line durvalumab plus chemotherapy and identify independent prognostic factors in patients with advanced BTC. Methods: This multicenter retrospective cohort study included patients with unresectable or metastatic BTC treated with first-line durvalumab plus chemotherapy across 21 tertiary oncology centers in Türkiye. Clinical characteristics, laboratory parameters, biomarker data, and treatment details were collected. The primary endpoint was overall survival (OS), while secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Survival outcomes were analyzed using the Kaplan–Meier method and Cox proportional hazards regression models. Results: A total of 78 patients were analyzed; 53.8% were male, and the median age was 62 years. Primary tumor sites were intrahepatic (55.1%), extrahepatic (30.8%), and gallbladder (14.1%). After a median follow-up of 12.58 months, median OS was 11.59 months and median PFS was 6.80 months. The ORR was 50.6%, including complete and partial responses in 2.7% and 47.9% of patients, respectively. Treatment-related adverse events occurred in 97.4% of patients, with grade 3–4 events in 37.2%. Immune-related adverse events were observed in 19.2%, including one case of grade 3 pneumonitis. No patient permanently discontinued durvalumab due to toxicity, and no durvalumab-related mortality occurred. In multivariable analysis, ECOG performance status 2 (HR 3.43; 95% CI 1.33–8.80) and ALBI grade 2–3 (HR 2.54; 95% CI 1.24–5.19) independently predicted worse OS, while ECOG performance status 2 also predicted shorter PFS (HR 5.91; 95% CI 2.30–15.17). Conclusions: In this multicenter real-world Turkish cohort, first-line durvalumab plus chemotherapy showed effectiveness and tolerability comparable to clinical trial data. Baseline ECOG performance status and ALBI grade were independent prognostic factors, supporting their use for risk stratification in advanced biliary tract cancer.