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.