Highlights
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First real-world multicentre data on adjuvant capecitabine in resected biliary tract cancer.
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Capecitabine showed a trend toward longer survival but no significant benefit on RFS/OS after IPTW adjustment.
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Nearly half of the patients required dose reductions; 36% discontinued treatment due to toxicity.
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This study highlights the need for new trials and translational research to personalize adjuvant BTC strategies.
Abstract
Background & Aims
Biliary tract cancers (BTCs) are rare, heterogeneous tumors associated with a poor prognosis, even after curative-intent surgery. Adjuvant capecitabine is currently the standard of care; however, real-world data on its efficacy and tolerance are lacking.
Patients and Methods
This French, retrospective, multicentre study, nested within the ACABi-PRONOBIL observational cohort, assessed adjuvant capecitabine efficacy in patients, with resected intrahepatic, perihilar, distal cholangiocarcinoma, or gallbladder carcinoma. who had not received prior systemic therapy. Patients treated with adjuvant capecitabine after 2017 were compared with patients diagnosed before 2017 and managed with surveillance only. The primary endpoint was overall survival (OS), secondary endpoints were recurrence-free survival (RFS) and toxicity. Inverse probability of treatment weighting (IPTW) in Cox regressions was used to adjust for measured confounding, imbalanced factors between groups.
Results
A total of 320 patients were included (197 in the capecitabine group and 123 in the surveillance group). In IPTW analysis, adjuvant capecitabine was not significantly associated with improved RFS (IPTW HR, 0.81, CI 95%, 0.54-1.21; p = 0.304), or OS (IPTW HR, 0.94, CI 95%, 0.58-1.52; p = 0.798). The point estimate for RFS was consistent with the ITT analysis of the BILCAP trial.
In the capecitabine group, 49% of patients required at least one dose reduction, and 35.7% discontinued treatment due to mainly grade 3/4 gastrointestinal (13.4%) and cutaneous (25.8%) toxicities.
Conclusions
In this real-world cohort, adjuvant capecitabine was not significantly associated with improved RFS or OS in patients undergoing curative-intent resection for BTC, although a numerical trend in favor of capecitabine for RFS. These findings support the need for refined patient selection strategies and for prospective evaluation of novel adjuvant approaches.
