Translational Research and New Technologies in Medicine and Surgery Department, Pisa University, Pisa, Italy.
Sant'Anna School of Advanced Studies, Pisa, Italy.
Liver Int. 2024 Oct;44(10):2763-2772. doi: 10.1111/liv.16047. Epub 2024 Jul 29.
The best adjuvant chemotherapy for resected biliary tract cancer (BTC) is under debate, with capecitabine supported by weak evidence. Aim of this network meta-analysis is to estimate the efficacy of different phase II/III regimens, comparing monotherapies (gemcitabine or fluoropyrimidines) head-to-head, against observation and combination regimens.
A comprehensive literature search was conducted on PubMed and EMBASE for phase II/III randomized clinical trials (RCTs) available as of December 2023, reporting hazard ratios (HRs) of overall survival (OS) and event-free survival (EFS). A frequentist framework employing a random-effects model was applied; treatment rankings were outlined according to P-score, based on direct and indirect evidence. Exploratory subgroup analyses for OS were also performed (primary site, resected margin status and nodal involvement).
Six RCTs (1979 total patients) were identified. Fluoropyrimidine monotherapy showed significantly better OS (HR .84 [.72-.97]) and EFS (HR .79 [.69-.91]) than observation, as any monotherapy did (HR .84 [.74-.96]; HR .79 [.70-.89]). In the head-to-head comparison for OS, only S1 confirmed to be superior to observation alone (HR .69 [.49-.98]) while fluoropyrimidines achieved the best P score (.81), similarly to any monotherapy (0.92). Combinations failed to prove superior to monotherapies with respect both to OS and EFS. Subgroup analyses were inconclusive due to results' inconsistency and limited sample size.
Our work confirmed that adjuvant chemotherapy grants OS and EFS benefit for resected BTC patients. Fluoropyrimidines appeared the most effective option, confirming capecitabine as the preferred choice for the Western population.
可切除胆管癌（BTC）的最佳辅助化疗方案仍存在争议，卡培他滨的疗效证据较为薄弱。本网状荟萃分析旨在比较单药（吉西他滨或氟嘧啶类）与观察和联合方案，评估不同 II/III 期方案的疗效。
对 PubMed 和 EMBASE 进行全面文献检索，纳入截至 2023 年 12 月发表的 II/III 期随机临床试验（RCT），报告总生存期（OS）和无事件生存期（EFS）的风险比（HR）。采用随机效应模型的频率派框架；根据直接和间接证据，基于 P 评分概述治疗排序。还对 OS 进行了探索性亚组分析（原发部位、切除边缘状态和淋巴结受累）。
共纳入 6 项 RCT（共 1979 例患者）。氟嘧啶类单药治疗的 OS（HR 0.84 [0.72-0.97]）和 EFS（HR 0.79 [0.69-0.91]）显著优于观察，任何单药治疗也如此（HR 0.84 [0.74-0.96]；HR 0.79 [0.70-0.89]）。在 OS 的头对头比较中，只有 S1 证实优于单独观察（HR 0.69 [0.49-0.98]），而氟嘧啶类药物的 P 评分最高（0.81），与任何单药治疗相似（0.92）。联合治疗在 OS 和 EFS 方面均未能优于单药治疗。由于结果不一致且样本量有限，亚组分析无法得出结论。
本研究证实辅助化疗可使可切除 BTC 患者获益。氟嘧啶类药物似乎是最有效的选择，证实卡培他滨是西方人群的首选。
