Comparison of Different First-Line Systemic Therapies in Advanced Biliary Tract Cancer Based on Updated Random Controlled Trials: A Systematic Review and Network Meta-Analysis

Abstract

Background and Aim. The prognosis of advanced biliary tract cancer (BTC) is relatively poor, with limited survival. Currently, the first-line standard of care treatment is gemcitabine plus cisplatin, whereas numerous trials are trying to explore new regimens and prolong the life span of these patients. Herein, we aim to compare the effectiveness of different treatments and conclude more promising regimens for patients with advanced BTC. Methods. We searched PubMed, Web of Science, and Cochrane Library for abstracts and full-text articles published from database inception through May 2022. All the random controlled trials (RCTs) were assessed and collected as eligible studies. The primary outcome was overall survival (OS). The second outcome was progression-free survival (PFS). Results. Seventeen studies, including 3632 patients, were selected from 1361 records. In the network meta-analysis for OS, gemcitabine + cisplatin (GemCis) + cediranib (HR, 0.11; 95% CI, 0.00-2.88), GemCis+durvalumab (HR, 0.27; 95% CI, 0.06-1.29), and GemCis + merestinib (HR, 0.37; 95% CI, 0.03-4.36) showed the trend of OS benefit over standard treatment (GemCis), although there was no significant difference. GemCis, GemOxa, and gemcitabine+S1 (GemS1) did not differ when comparing OS. In the network meta-analysis for PFS, GemCis+merestinib (HR, 0.67; 95% CI, 0.54-0.83) and GemCis+durvalumab (HR, 0.22; 95% CI, 0.08-0.62) showed PFS benefit over standard treatment (GemCis) with a significant difference. GemCis, GemOxa, and GemS1 did not differ when comparing PFS. Conclusion. GemCis+durvalumab might be the most promising regimen for advanced BTC when considering OS and PFS. GemOxa and GemS1 could be alternative options for advanced BTC patients with nontolerance to GemCis.