Efficacy and safety of adding S-1 to chemotherapy regimens in advanced gastric cancer: A meta-analysis.

Abstract

e16074 Background: Gastric cancer (GC) remains a major global health burden, ranking as the fifth most commonly diagnosed malignancy and the fifith leading cause of cancer-related mortality worldwide. Due to the lack of population-based screening programs, early detection is difficult and most patients are diagnosed with advanced disease, for whom curative treatment options are limited. S-1 is an oral fluoropyrimidine that has demonstrated encouraging efficacy and safety profiles for Advanced GC (AGC) S-1-containing regimens by several randomized controlled trials (RCTs). This review aims to evaluate whether S-1-based chemotherapy regimens improve survival and disease progression outcomes in AGC patients compared with non-S-1 strategies. Methods: A systematic search was conducted in the Medline, Cochrane, and Web of Science databases were systematically searched for RCTs comparing S-1 containing regimens with other treatments without S-1 in patients diagnosed with AGC. The assessed outcomes included Progression-Free Survival (PFS), Overall Survival (OS), Overall Response Rate (ORR), Disease Control Rate (DCR), Time to Progression (TTP), Time to Treatment Failure (TTF), as well as all grades and ≥ 3 grade Adverse Events (AEs). The assessed outcomes with 95% Confidence Intervals (CI) were estimated using random-effects models. Heterogeneity among studies was assessed using the I² statistic. Statistical analyses were performed using RStudio 4.4.2. Results: A total of 20 RCTs encompassing 3,181 patients were included in the meta-analysis, from whom 1,665 received S-1-containing regimens and 1,516 received control treatments. The pooled analysis demonstrated a statistically significant improvement in PFS (HR: 0.8778; 95% CI: 0.7855-0.9808; p: 0.02; I²: 38.3%) and OS (HR: 0.9260; 95% CI 95%: 0.8595-0.9976; p: 0.04; I²: 0.0%) in S-1 containing treatments. Regarding tumor response outcomes, no statistically significant differences were observed in ORR (OR: 1.17; 95% CI: 0.86-1.58; p: 0.31; I²: 62.5%) and DCR (OR: 1.18; 95% CI: 0.92-1.53; p: 0.22; I²: 0%). Time-to-event secondary endpoints showed a significant prolongation of TTF (HR: 0.83; 95% CI: 0.74-0.94), whereas no significant difference was observed in TTP (HR: 1.04; 95% CI: 0.85-1.26). Conclusions: S-1-containing regimens improved PFS and TTF and showed a borderline OS benefit without increasing adverse events, although no significant differences were observed in tumor response outcomes.These findings suggest that S-1-based strategies for AGC patients may offer a modest survival benefit without increased toxicity.