Comparative efficacy and safety of S-1 plus oxaliplatin with sintilimab vs. paclitaxel-S-1-oxaliplatin and docetaxel-oxaliplatin-5-fluorouracil as first-line therapy for advanced gastric cancer.

This study compared the efficacy and safety of S-1 + oxaliplatin (SOX) plus sintilimab, albumin-bound paclitaxel + oxaliplatin (P-SOX), and docetaxel + oxaliplatin + 5-fluorouracil (DOF) as neoadjuvant regimens for advanced gastric cancer. We retrospectively analyzed 289 patients who received neoadjuvant and adjuvant chemotherapy followed by standard D2 radical gastrectomy (SOX + sintilimab, n  = 81; P-SOX, n  = 128; DOF, n  = 80). Patients were randomly divided 7 : 3 into training and validation sets. Short-term efficacy, long-term outcomes, and adverse events were evaluated, and predictors of progression-free survival (PFS) were explored. The objective response rate of SOX + sintilimab was 91.36% by tumor regression grade (TRG) and 70.37% by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), numerically higher than P-SOX (88.38 and 59.20%) and DOF (86.25 and 57.50%) without significance (TRG, P  = 0.587; RECIST 1.1, P  = 0.178). Median overall survival (OS) was 32 months [95% confidence interval (CI): 30.00-not reached] with SOX + sintilimab, superior to P-SOX (28 months; 95% CI: 26.00-31.00) and DOF (26 months; 95% CI: 23.00- 32.00) ( P  = 0.007). Median PFS was 30 months (95% CI: 27.00-33.00) for SOX + sintilimab, 25 months (95% CI: 22.00-26.00) for P-SOX, and 22.5 months (95% CI: 19.00-26.00) for DOF ( P  = 0.096). Common adverse events included grade 1-2 gastrointestinal reactions, peripheral neurotoxicity, and alopecia, with good tolerability. SOX plus sintilimab achieved the most favorable OS with comparable safety.