Real-world effectiveness of durvalumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin in advanced gallbladder cancer: a study using the TriNetX global network.

BACKGROUND

Gallbladder cancer (GBC) represents a rare but aggressive malignancy, often diagnosed at an advanced stage. Although immune checkpoint inhibitors have improved outcomes in biliary tract cancers, GBC-specific evidence remains limited due to underrepresentation in pivotal clinical trials.

OBJECTIVES

To evaluate the real-world effectiveness and safety of durvalumab combined with gemcitabine and cisplatin (Durva + gemcitabine and cisplatin (GemCis)) compared to GemCis alone in patients with advanced GBC.

DESIGN

Retrospective, multi-institutional cohort study.

METHODS

Data were collected from the TriNetX Global Collaborative Network. Adults diagnosed with advanced GBC between January 2020 and January 2025 who received Durva + GemCis or GemCis as first-line therapy were included. Propensity score matching (1:1) was performed based on age, sex, race, metastatic sites, and tumor marker levels. The primary outcome was overall survival (OS), whereas secondary outcomes included adverse events (AEs).

RESULTS

Among 2458 patients with advanced GBC, 130 received Durva + GemCis and 201 received GemCis. After matching, 111 patients per group were analyzed. Median OS was significantly longer in the Durva + GemCis group compared to the GemCis group (13.1 vs 8.5 months; log-rank p = 0.028). Most AEs were comparable between groups; however, malaise and fatigue were more frequently reported in the Durva group (28.8% vs 16.2%; hazard ratio: 1.98, 95% confidence interval: 1.11-3.53).

CONCLUSION

In this real-world study, the addition of durvalumab to GemCis was associated with improved OS in patients with advanced GBC, with a manageable safety profile. These exploratory findings should be interpreted with caution, underscoring the need for dedicated GBC-specific prospective trials.