Exploring the impact of durvalumab on biliary tract cancer: insights from real-world clinical data

Abstract

Introduction: This study assesses the effectiveness of durvalumab with platinum and gemcitabine for biliary tract cancers (BTC). It aims to confirm the TOPAZ-1 trial results in a real-world context and explore the link between BTC molecular profiles and patient outcomes.

Methods: A retrospective analysis was conducted on 102 BTC patients treated with durvalumab, platinum, and gemcitabine at five cancer centers in Austria and one in Germany from 2022 to 2024. Molecular profiling used targeted DNA and RNA assays. Clinical endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed using log-rank tests and Cox regression, with correlations to second-line molecular-targeted therapies.

Results: Among 102 patients, 60.8% had intrahepatic cholangiocarcinoma. The treatment achieved a disease control rate of 71.57% and an overall response rate of 35.11%. Median PFS was 6.51 months, and OS was 13.61 months. Patients under 65 had significantly better OS. Alterations in chromatin remodeling or homologous recombination repair genes were not predictive of survival benefit (HR: 0.45; p = 0.851 and HR: 1.63; p = 0.26, respectively). Patients with molecular-informed second-line therapy showed a trend toward survival benefit (HR: 0.23; p = 0.052).

Conclusion: This study confirms the phase 3 trial results of durvalumab with platinum and gemcitabine, providing a substantial real-world dataset with detailed molecular characterization. No specific patient subgroup showed a markedly better response to durvalumab based on conventional NGS panels. Further research is needed to explore the link between immunotherapy responses and molecular subgroups.

Keywords: Biliary tract cancer; Chromatin remodeling; Durvalumab; Homologous recombination repair (HRR); Molecular-informed therapy; Precision oncology.

Fig. 1

Study profile. The number of patients (n) at key target points is indicated; BTC, biliary tract cancer

Fig. 2

Oncoplot diagram of all patients. All types of detected mutations are indicated, including insertions, deletions, frameshift alterations, splice site, nonsense and missense mutations. Each column represents an individual patient and each row an individual gene. The right column displays the number of patients carrying mutations in these genes along with the corresponding percentage

Fig. 3

Response Rates and Kaplan–Meier curves illustrating progression-free survival (PFS) and overall survival (OS) of the total cohort

Fig. 4

Univariate analysis of OS across clinical subgroups. The plot shows median OS (months) with 95% confidence intervals (CI), hazard ratios (HR) from univariate Cox regression, and associated p-values. Age < 65 years was significantly associated with improved OS; other factors, including tumor localization, sex, ECOG status, resection, stage, and adjuvant treatment, were not significant

Fig. 5

Response rates and Kaplan Meier curves comparing HRRm and non-HRRm patients exposed to durvalumab + platinum doublet

Fig. 6

Response rates and Kaplan Meier curves comparing patients with alterations in chromatin remodeling genes exposed to durvalumab + platinum doublet

Fig. 7

Kaplan Meier curves comparing FOLFOX vs FOLFIRI in 2nd line after durvalumab + platinum-based doublet (left). Application of molecular-matched therapies in 2nd line and beyond post-progression on durvalumab + platinum-based doublet (right)