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

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-03-07 DOI:10.1016/j.ejca.2025.115342

Erman Akkus , Angela Lamarca

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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

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.