Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis using reconstructed RCT survival data

作者：Zhihao Li, Daniel Aliseda, Owen Jones, Luckshi Rajendran, Christian Tibor Josef Magyar, Robert Grant, Grainne M. O’Kane, Anna Saborowski, Gonzalo Sapisochín, Arndt Vogel · 发表于：JHEP Reports · 年份：2024 · DOI：10.1016/j.jhepr.2024.101290 · 被引用次数：20 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Gallbladder and Bile Duct Disorders、Liver Diseases and Immunity

Gemcitabine/cisplatin (GemCis) was the long-standing first-line treatment for advanced biliary tract cancers (BTCs). Following positive results from the TOPAZ-01 and KEYNOTE-966 trials, immune checkpoint inhibitors (ICIs) combined with chemotherapy are now the standard of care. We aim to compare the efficacy of first-line therapies for advanced BTCs. Our systematic review included studies from five databases focusing on English-language articles published between January 2010 and June 2024. We included randomized clinical trials (RCTs) that featured GemCis in a treatment arm for treatment-naive adults with advanced BTCs. The primary endpoints were overall survival (OS) and progression-free survival. We conducted a one-stage meta-analysis using reconstructed survival data, Cox-based models, and restricted mean survival time (RMST). After screening 8,797 studies, 17 RCTs were selected, involving a total of 4,584 patients. Of these, 2,140 (46.7%) received GemCis. The majority (68.9%) were diagnosed with intrahepatic or extrahepatic cholangiocarcinoma, and 80% had metastatic disease at the time of treatment. The pooled median OS in the GemCis group was 11.6 months (95% CI 11.3–12.2 months). GemCis plus pembrolizumab (hazard ratio [HR] 0.99, 95% CI 0.98–0.99; p <0.001), GemCis plus durvalumab (HR 0.98, 95% CI 0.97–0.99; p = 0.015), GemCis plus S-1 (HR 0.97 95% CI 0.95–0.99; p <0.001), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.98–0.99; p <0.001) demonstrated superior OS com...