Adjuvant durvalumab or tislelizumab combined with S-1 for resected high-risk biliary tract cancers in China: A multicenter, two-cohort, single-arm, open-label, phase 2 trial preliminary analysis.

Abstract

e16275 Background: Patients with biliary tract cancer (BTC) have a poor prognosis and high postoperative recurrence rates. Immunochemotherapy has been approved as a first-line treatment for advanced BTC. We aimed to explore the efficacy and safety of durvalumab (an anti-PD-L1 immunotherapy) or tislelizumab (an anti-PD-1 immunotherapy) combined with S-1 chemotherapy as a postoperative adjuvant treatment in patients at high risk of BTC recurrence. Methods: This was a multicentre, two-cohort, single-arm, phase 2 trial in BTC patients with R0-resected at high-risk recurrence. The study was being conducted at 2 tertiary hospitals in China. Patients received eight 21-day cycles of durvalumab or tislelizumab plus S-1. Following S-1 discontinuation, maintenance therapy with durvalumab or tislelizumab alone was administered in 28-day cycles for a maximum of 6 cycles. Propensity score matching (PSM) (1:2) analysis was used to balance potential bias. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included overall survival (OS) and safety. Survival was assessed in the full analysis set (FAS) and safety was assessed in the safety set. This study is registered with ClinicalTrials.gov (NCT06490107) and is currently ongoing but no longer recruiting new patients. Results: Between Jun 4, 2024, and Jan 10, 2026, 54 patients with BTC were enrolled: 40 in the durvalumab plus S-1 cohort and 14 in the tislelizumab plus S-1 cohort. At the data cutoff of Jan 12, 2026, the median follow-up period was 12.75 months (95% confidence interval [CI], 8.25-17.24) and 14 (26%) patients had recurrence. The median RFS and OS of all patients were not reached. In FAS, 1-year RFS rate was 62.2% (95% CI, 48.0-80.7) and 1-year OS rate was 92.9% (95% CI, 83.5-100). 1-year RFS rate was 62.9% (95% CI, 47.3-83.5) and 1-year OS rate was 94.1% (95% CI, 83.6-100) with durvalumab plus S-1. 1-year RFS rate was 59.3% (95% CI, 32.2-100) and 1-year OS rate was 87.5% (95% CI, 67.3-100) with tislelizumab plus S-1. No significant differences in RFS and OS were observed between two cohorts, both before (p = 0.733) and after PSM (p = 0.939). The most common treatment-related adverse events (TRAEs) were neutropenia (41%), increased AST/ALT (33%), rash (30%), nausea (28%), pigmentation (28%). Grade 3 TRAEs occurred in 15 (28%) patients, including neutropenia (n = 5), rash (n = 3), pruritus (n = 2), increased AST/ALT (n = 2), elevated bilirubin concentrations (n = 2), diarrhoea (n = 1). No grade 4 TRAEs or treatment-related deaths occurred. Conclusions: Adjuvant therapy with S-1 combined with either durvalumab or tislelizumab demonstrates promising efficacy with an acceptable safety profile in patients with resected BTC at high risk recurrence. Further validation of this immunochemotherapy regimen is warranted in larger, multicentre trials. Clinical trial information: NCT06490107 .