Should S-1 be better than capecitabine for patients with advanced gastric cancer in Asia? A systematic review and meta-analysis

BACKGROUND: S-1 or capecitabine (Cap) containing treatment is an increasingly used strategy in patients with advanced gastric cancer in Asia. It is unclear whether there is sufficient evidence to support which regimen is better. METHODS: A systematic review of retrospective studies and randomized controlled trials (RCTs) comparing S-1 with Cap containing treatment in advanced gastric cancer patients was performed. Embase, PubMed, ClinicalTrials.gov, Cochrane Library, and reference lists were searched from inception until August 2018 for relevant studies. Outcomes of interest included 1-year overall survival (OS), 1-year progression-free survival (PFS), objective response rate (ORR), and adverse events. Meta-analyses of the random events were performed. We also performed sensitivity analysis to examine whether the results of the meta-analyses were robust. RESULTS: A total of 770 subjects from six RCTs and two retrospective studies in Asia were analyzed. Compared with S-1, Cap containing treatment had better ORR (overall risk ratio =0.85, 95% CI: 0.72, 0.99, I(2)=0%, P=0.043) and higher incidence of all-grade hand-foot syndrome (HFS) (overall risk ratio =0.29, 95% CI: 0.20, 0.40, I(2)=0%, P<0.001) and neutropenia (overall risk ratio =0.85, 95% CI: 0.73, 0.99, I(2)=0%, P=0.039). But there was no statistical difference in 1-year PFS, 1-year OS, incidence of other all-grade or grade 3–4 adverse events between S-1 and Cap containing arms (P>0.05). We found no publication bias in this review. CONCLUSION: This systematic review showed that for Asian patients, Cap shows superiority in ORR but not 1-year OS or PFS, and it will increase the risk of all-grade HFS and neutropenia. Until now, S-1 containing treatment might be a better choice for advanced gastric cancer patients. But more high-quality RCTs are needed to confirm these results.