辅助化疗与手术切除的胆管癌观察治疗对比：III期随机对照试验的生存meta分析

Adjuvant chemotherapy compared to observation in resected biliary tract cancers: Survival meta-analysis of phase-III randomized controlled trials.

作者信息

Akkus Erman, Lamarca Angela

机构信息

Ankara University Faculty of Medicine, Department of Medical Oncology, Ankara, Türkiye; Ankara University Cancer Research Institute, Ankara, Türkiye.

Department of Oncology, OncoHealth Institute, Instituto de Investigaciones Sanitarias FJD, Fundación Jiménez Díaz University Hospital, Madrid, Spain.

出版信息

Eur J Cancer. 2025 May 2;220:115342. doi: 10.1016/j.ejca.2025.115342. Epub 2025 Mar 7.

DOI:10.1016/j.ejca.2025.115342

PMID:40101432

Abstract

BACKGROUND

A limited number of randomized controlled trials (RCTs) investigated adjuvant chemotherapy in biliary tract cancers (BTCs). Recurrences and deaths are common in the first 2 years and survival remains poor despite adjuvant treatment.

METHODS

Phase-III RCTs were included comparing adjuvant chemotherapy and observation in resected BTCs. The primary endpoints were recurrence-free (RFS) and overall survival (OS). Proportional hazard results were used for trial-based analyses. Patient data was curated from published Kaplan-Meier curves to analyze short-term (2-year) hazards. The Parmar and generic inverse variance methods were used.

RESULTS

1308 patients in 4 trials (BILCAP, ASCOT, BCAT, PRODIGE-12) were included. Capecitabine (BILCAP) and S-1 (ASCOT) were grouped as 5-FU-based, gemcitabine (BCAT) and gemcitabine-oxaliplatin (PRODIGE-12) were grouped as gemcitabine-based chemotherapy. Adjuvant 5FU-based chemotherapy improved RFS [HR: 0.80 (95 % CI:0.68-0.95), p = 0.012] and OS [HR: 0.78 (95 % CI:0.65-0.94), p = 0.009]. However, gemcitabine-based chemotherapy did not provide benefit in RFS [HR: 0.90 (95 % CI:0.70-1.15), p = 0.428] and OS [HR: 1.03 (95 % CI:0.78-1.36), p = 0.794]. The benefit of 5-FU-based chemotherapy was more apparent in the short-term (2-year hazards) (RFS: [HR: 0.67 (95 %CI:57-0.79), p < 0.001] and OS: [HR: 0.61 (95 % CI:59-0.64), p < 0.001]). However, gemcitabine-based chemotherapy did not provide RFS benefit in the short term either [HR: 0.80 (95 % CI:0.64-0.1.01), p = 0.067] and seemed to be even detrimental for OS [HR: 1.22 (95 % CI:1.14-1.31), p < 0.001] in the first 2 years.

CONCLUSION

This study confirms using 5FU-based monotherapy in the adjuvant treatment of resected BTCs. The more prominent benefit in the first 2 years emphasizes that more effective adjuvant treatments with sustained long-term benefits are needed. Two-year proportional hazards OS and RFS are proposed here as an additional secondary end-point to consider in future clinical trials. in this setting. Registration ID (PROSPERO): CRD42024614444.

摘要

背景

仅有少数随机对照试验（RCT）研究了胆道癌（BTC）的辅助化疗。复发和死亡在前两年很常见，尽管进行了辅助治疗，但生存率仍然很低。

方法

纳入了比较切除的BTC患者辅助化疗与观察的III期RCT。主要终点是无复发生存期（RFS）和总生存期（OS）。基于比例风险结果进行基于试验的分析。从已发表的Kaplan-Meier曲线中整理患者数据，以分析短期（2年）风险。使用了Parmar法和通用逆方差法。

结果

纳入了4项试验（BILCAP、ASCOT、BCAT、PRODIGE-12）中的1308例患者。卡培他滨（BILCAP）和S-1（ASCOT）被归为基于5-氟尿嘧啶（5-FU）的化疗，吉西他滨（BCAT）和吉西他滨-奥沙利铂（PRODIGE-12）被归为基于吉西他滨的化疗。辅助性基于5-FU的化疗改善了RFS [风险比（HR）：0.80（95%置信区间：0.68 - 0.95），p = 0.012] 和OS [HR：0.78（95%置信区间：0.65 - 0.94），p = 0.009]。然而，基于吉西他滨的化疗在RFS [HR：0.90（95%置信区间：0.70 - 1.15），p = 0.428] 和OS [HR：1.03（95%置信区间：0.78 - 1.36），p = 0.794] 方面未显示出益处。基于5-FU的化疗的益处在短期（2年风险）更为明显（RFS：[HR：0.67（95%置信区间：0.57 - 0.79），p < 0.001] 和OS：[HR：0.61（95%置信区间：0.59 - 0.64），p < 0.001]）。然而，基于吉西他滨的化疗在短期内也未提供RFS益处 [HR：0.80（95%置信区间：0.64 - 1.01），p = 0.067]，并且在前两年似乎对OS甚至有害 [HR：1.22（95%置信区间：1.14 - 1.31），p < 0.001]。