Combination versus mono-therapy as salvage treatment for advanced biliary tract cancer: A comprehensive meta-analysis of published data

Abstract

Gemcitabine-based chemotherapy regimens remain the standard first-line treatment for advanced biliary tract cancers (BTCs) patients with no second-line treatments established yet. The preset meta-analysis aims to comprehensively evaluate the role of second-line treatment for advanced BTCs in terms of response, overall survival and toxicities. Eligible studies were identified using Medline, Pubmed, and meeting abstracts. Searches were last updated on April 30, 2018. Eligible studies reported survival and/or response data for refractory BTCs patients receiving second-line therapy. Primary outcomes of interest were objective response rate (ORR), disease controlled rate (DCR), 1-year overall survival (OS), and progression free survival (PFS). A total of 38 cohorts from 32 studies were eligible for analysis: 23 prospective phase II trials and 9 retrospective studies. In total, data from 1391 patients were reported with median number of patients included in each cohort of 28.5 (range: 9-255). The weighted median PFS and OS for refractory BTCs received second-line therapy were 2.6 months and 6.5 months, respectively. Fluoropyrimidine-based, gemcitabine-based, or Taxanes-based chemotherapy was not superior to single targeted/toxic agent in terms of ORR. In addition, the pooled disease control rate (DCR) and 1-year overall survival (OS) of fluoropyrimidine-based chemotherapy was inferior to single targeted/toxic agent (DCR: 47% versus 60%, RR 0.78, 95%CI: 0.61-1.00, p = 0.03; 1-year OS: 15% versus 29.6%, RR 0.90, 95%CI: 0.29-0.87, p = 0.006), but not for GEM-based or taxanes-based chemotherapy. In addition, correlation analysis indicates that the best correlations were between median OS and median PFS for all cohorts (r=0.57; P = 0.003). Combined second-line treatment is not superior to single targeted/toxic agent as salvage treatment for advanced BTCs in terms of ORR, DCR and 1-year OS, and fluoropyrimidine-based chemotherapy seems to be inferior to other second-line regimens. With available evidence from published data, we could not clearly recommend a preferred second-line regimen for advanced BTCs. Further prospective randomized studies are needed to confirm our findings and investigate more efficient second-line therapy in this setting.