Systematic review and non-inferiority meta-analysis of randomised phase II/III trials on S-1-based therapy versus 5-fluorouracil- or capecitabine-based therapy in the treatment of patients with metastatic colorectal cancer

Abstract

BackgroundS-1 is an oral fluoropyrimidine that is increasingly used in Western countries for the treatment of metastatic colorectal cancer (mCRC). We conducted a non-inferiority meta-analysis on the efficacy of S-1-based therapy versus 5-fluorouracil (5-FU)- or capecitabine-based therapy in the treatment of patients with mCRC. MethodsMEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Opengrey were searched for randomised clinical trials until May 2021. Data were extracted for progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and adverse events. Pooled effect estimates, stratified by treatment line, with corresponding 99% confidence intervals (CI) were presented. For PFS, a pre-defined non-inferiority margin (ΔNI) of 1.25 was selected. ResultsTen studies (n = 2117) were included, of which six studies reported PFS and OS data and 10 studies reported ORR data. S-1-based therapy was shown to be non-inferior to 5-FU/capecitabine-based therapy in terms of PFS (HRtotal 0.95, 99% CI 0.83–1.08) with its CI upper limit well below ΔNI, and at least as efficacious in terms of OS (HRtotal 0.93, 99% CI 0.81–1.07), and ORR (RRtotal 1.06, 99% CI 0.90–1.24). ConclusionsS-1-based therapy is non-inferior to 5-FU/capecitabine-based therapy in the treatment of mCRC regarding PFS and at least as efficacious as 5-FU/capecitabine-based therapy in terms of ORR and OS. These data support the use of S-1 in mCRC patients who are intolerant to 5-FU/capecitabine-based treatment.