TY - JOUR
T1 - 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
AU - Derksen, Jeroen W. G.
AU - Smit, Karel C.
AU - May, Anne M.
AU - Punt, Cornelis J. A.
N1 - Funding Information: The current work was supported by an unrestricted scientific grant from Nordic Pharma . Publisher Copyright: © 2022 The Author(s)
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Background: S-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. Methods: MEDLINE, 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. Results: Ten 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). Conclusions: S-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.
AB - Background: S-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. Methods: MEDLINE, 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. Results: Ten 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). Conclusions: S-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.
KW - Fluoropyrimidines
KW - Meta-analysis
KW - Metastatic colorectal cancer
KW - Non-inferiority
KW - S-1
KW - Treatment
UR - http://www.scopus.com/inward/record.url?scp=85125888187&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ejca.2022.02.004
DO - https://doi.org/10.1016/j.ejca.2022.02.004
M3 - Review article
C2 - 35279472
SN - 0959-8049
VL - 166
SP - 73
EP - 86
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -