Survival outcomes of Durvalumab in combination to cisplatin and gemcitabine in advanced biliary tract cancer: real world results from a single Italian institution

Introduction: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a retrospective analysis of its first-line treatment outcomes. Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with cisplatin, gemcitabine plus durvalumab. The primary endpoint was overall survival (OS). RESULTS: 33 patients were enrolled. Median OS was NR and median PFS was 7.6 months, after a median follow up of 13.5 months. The investigator-assessed overall response rate was 34.5 %, with stable disease in 53.0 % of patients. High baseline CEA levels were associated with poor survival. Any grade adverse events (AEs) occurred in 97 % of patients. Immune-related AEs (irAEs) occurred in 16 % (grade >2: 6 %). Presence of TP53 mutation was related to a worse OS, conversely the presence of ARID1A genomic alteration was related to a better PFS. A tendence toward a better OS was found for BRCAness patients which did not reach the statistical significance. On the other hand, BRCAness patients showed significantly higher PFS compared to no BRCAness patients Conclusion: This real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.