tumour-expression predicts benefits from capecitabine in the BILCAP phase III randomized adjuvant trial

Abstract

Background: The BILCAP trial showed benefit in relapse-free survival (RFS) and overall survival (OS) from adjuvant capecitabine in patients(pts) with resected biliary tract cancers (BTC). In this post-hoc analysis we evaluated the role of CD80 expression, a surface ligand expressed by Antigen Presenting Cells, as a predictive biomarker of adjuvant therapy efficacy in the BILCAP trial. Method(s): Central (C) and Invasion Front (IF) tumour-regions (3 cores each) from resected BTC were used to generate Tissue Microarrays from the BILCAP pts (iCCA=60, eCCA=199, GBC=47). CD80 expression was assessed by immunohistochemistry and scored as number of positive cells/2mm2. Mean of the 3 cores was obtained and averaged in the CD80 CIF-score (mean of C + mean of IF)/2]. Maximally-Selected-Rank-Statistics and subgroup analyses were performed to determine the best predictive value of the score. Kaplan-Meier method was applied for survival analysis. Result(s): CD80 CIF score was evaluated in 304 pts (n=153 treatment arm, n=151 observation arm). This cohort reflected the outcomes of the BILCAP trial. CD80-CIF score 40 RFS (p:0.3); OS (p:0.7)]. Although the BILCAP study was not sufficiently powered to detect differences across BTC- subtypes, a trend was observed for benefit from capecitabine only in low CD80-CIF score for eCCA and GBC. However, iCCA displayed lower values of CD80-CIF and its predictive cut-off had to be adjusted; iCCA pts with a CD80-CIFscore>=5, exhibited a remarkably improved mRFS (37 vs. 6 mo) and mOS (91 vs. 17 mo), capecitabine vs observation. Conclusion(s): CD80-CIF score<=40 appears a potential predictive biomarker of capecitabine efficacy in pts with resected BTC. For iCCA, the cutoff may need changing for a better performance, due to different immune environment. Legal entity responsible for the study: The authors. Funding(s): The lab of Chiara Braconi has been supported by Chief Scientist Office (TCS/21/25), University of Glasgow (Lord Kelvin Adam Smith Readership; Welcome Trust-Institutional ISSF Excellent and Catalyst award 31038), the CRUK-Scotland Cancer Centre (CTRQQR-2021/100006), AMMF (322067) Avacta (316813), Servier (320463) and Medannex (318434), Cancer Research UK Scotland Institute Core Award (SEBINT-2024/100001). Disclosure: M. Rofei: Financial Interests, Personal, Research Grant: Precision BTC. V. Formica: Financial Interests, Personal, Invited Speaker: Merck, Servier, Amgen, Pierre Fabre. M. Fassan: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Invited Speaker: Sanofi, Eli Lilly, Bristol Meyer Squibb, Pfizer, Sanofi, Astellas, AstraZeneca, Diapath, GSK, Roche, Pierre Fabre, Novartis, MSD, Incyte, IQVIA, Janssen Pharma. V.E. Crolley: Financial Interests, Invited Speaker: AstraZeneca. G. Tesini: Financial Interests, Invited Speaker: AstraZeneca. J.A. Bridgewater: Financial Interests, Funding: Incyte; Financial Interests, Invited Speaker: Incyte, Servier, AstraZeneca, BMS; Financial Interests, Other: AstraZeneca, Beigene, Taiho. C. Braconi: Financial Interests, Invited Speaker: AstraZeneca, Incyte; Financial Interests, Other: Servier, Boehringer Ingelheim, Tahio, Jazz Pharmaceutic, Molecular Partners, AstraZeneca; Financial Interests, Funding: Avacta, Medannex, Servier. All other authors have declared no conflicts of interest.Copyright © 2025