Adjuvant Chemotherapy Regimens in Resected Biliary Tract Cancers: National, Comparative, Observational Study (TOG/GI-SAFRADJU-2501)

Abstract

The recommended adjuvant chemotherapy (adj-ChT) regimen for resected biliary tract cancers (BTC) is capecitabine (Cape); yet, the recommendation is based on limited evidence. Although varied adj-ChTs have been employed in practice, robust real-world data is scarce. We conducted a national, multicenter, hospital-based registry study to evaluate adj-ChTs in resected BTCs. Patients who received adj-ChT (± radiotherapy) between 2010 and 2024 were included. Recurrence-free (RFS) and overall survival (OS) were analyzed by adjusted Cox-regression and propensity score-based inverse-probability-of-treatment-weighting (IPTW), addressing selection bias. Among 617 patients from 44 centers, 513 were eligible. The most frequent adj-ChTs were Cape (35.5% [n = 182]), gemcitabine–cisplatin (Gem-Cis; 22.4% [n = 115]), gemcitabine–capecitabine (Gem-Cape; 20.1% [n = 103]), and gemcitabine (Gem; 10.7% [n = 55]). Median RFS and OS with Cape were 19.7 (95% Confidence Interval [95% CI]: 14.2–41.1) and 41.9 months (95% CI: 25.9–69.2). In adjusted/controlled comparisons with Cape, no differences in RFS or OS were observed with Gem-Cis (RFS: Hazard Ratio [HR] 1.13 [95% CI: 0.77–1.66]; OS: HR: 1.03 [95% CI: 0.66–1.61]), Gem-Cape (RFS: HR 0.97 [95% CI: 0.68–1.38]; OS: HR: 0.81 [95% CI: 0.52–1.24]), or Gem (RFS: HR 1.00 [95% CI: 0.63–1.59]; OS: HR: 0.93 [95% CI: 0.55–1.57]). Similarly, IPTW analyses showed no difference in RFS and OS. Radiotherapy appeared to be associated with improved survival. Performance status, T-stage, lymph-node positivity, and R1-resection were independently associated with RFS and OS. In conclusion, this real-world study did not identify a regimen superior to Cape. Given the modest benefit of adj-ChTs, novel approaches, including neoadjuvant and targeted/immunotherapy strategies, are needed.