Individual patient data meta-analysis of adjuvant gemcitabine-based chemotherapy for biliary tract cancer: combined analysis of the BCAT and PRODIGE-12 studies

Julien Edeline, Satoshi Hirano, Aurélie Bertaut, Masaru Konishi, Meher Benabdelghani, Katsuhiko Uesaka, Jérôme Watelet, Masayuki Ohtsuka, Pascal Hammel, Yuji Kaneoka, Jean Paul Joly, Masakazu Yamamoto, Laure Monard, Yoshiyasu Ambo, Christophe Louvet, Masahiko Ando, David Malka, Masato Nagino, Jean Marc Phelip, Tomoki Ebata

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background: Although gemcitabine-based chemotherapy is the standard of care for advanced biliary tract cancers (BTCs), adjuvant phase III studies (BCAT in Japan, PRODIGE 12 in France) failed to show benefit, possibly owing to fewer patients (n = 225 and n = 194) compared with the adjuvant capecitabine BILCAP trial (n = 447). We performed a combined analysis of both gemcitabine-based chemotherapy adjuvant studies. Methods: We performed individual patient data meta-analysis of all patients included in BCAT and PRODIGE 12. BCAT study randomised patients with extrahepatic cholangiocarcinoma to single-agent gemcitabine or observation. PRODIGE 12 randomised patients with all BTC subtypes to gemcitabine-oxaliplatin combination or observation. Combined analysis was performed using Kaplan–Meier curves and a Cox regression model stratified on the trial. Results: Two hundred and twelve versus 207 patients were randomised in the gemcitabine-based chemotherapy versus observation arms. Baseline characteristics were balanced between arms. The median follow-up was 5.5 years. After 258 relapse-free survival (RFS) events, there was no difference in RFS (log-rank p = 0.45; hazard ratio [HR] = 0.91 [95% confidence interval [CI] 0.71–1.16]; p = 0.46). RFS rates at five years were 40.8% (95%CI: 33.9%–47.5%) for gemcitabine-based chemotherapy versus 36.6% (95%CI: 29.8%–43.4%) for observation. After 201 deaths, there was no difference in overall survival (OS) (log-rank p = 0.83; HR = 1.03 [95%CI: 0.78–1.35]; p = 0.85). OS rates at five years were 50.5% (95%CI: 43.1%–57.4%) for gemcitabine-based chemotherapy versus 49.3% (95%CI: 41.6%–56.5%) for observation. Conclusion: With 419 patients included, this analysis did not show significant improvement in RFS and no trend in improvement in OS. Gemcitabine-based chemotherapy should not be used as an adjuvant treatment for BTC.

Original languageEnglish
Pages (from-to)80-87
Number of pages8
JournalEuropean Journal of Cancer
Volume164
DOIs
StatePublished - Mar 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Ltd

Funding

The PRODIGE 12 study was funded by the Programme Hospitalier de Recherche Clinique (PHRC 2009) and the Ligue Nationale Contre le Cancer . The BCAT trial was supported by funding from the Nagoya Surgery Support Organisation and Eli Lilly Japan K.K., which had no role in the study design, data collection, data analysis or data interpretation.

FundersFunder number
Nagoya Surgery Support Organisation
Eli Lilly Japan
Ligue Contre le Cancer

    Keywords

    • Adjuvant treatment
    • Biliary tract cancer
    • Chemotherapy
    • Cholangiocarcinoma
    • Gemcitabine

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