Published online Aug 15, 2025. doi: 10.4251/wjgo.v17.i8.109646
Revised: June 2, 2025
Accepted: July 1, 2025
Published online: August 15, 2025
Processing time: 89 Days and 12.1 Hours
Gastric cancer (GC) remains a major global health burden, particularly in East Asia, due to its high incidence, aggressive progression, and poor prognosis in advanced stages. Although surgery is the mainstay of curative treatment, outcomes for locally advanced cases remain unsatisfactory despite perioperative chemotherapy. In recent years, immune checkpoint inhibitors, especially anti-PD-1 antibodies like sintilimab, have shown promise in improving survival when combined with chemotherapy. However, the comparative efficacy and safety of SOX plus sintilimab vs established regimens such as P-SOX and SOX alone in the neoadjuvant setting have not been fully explored.
To compare the efficacy and safety of three neoadjuvant chemotherapy regimens—SOX combined with sintilimab (SOX + PD-1), albumin-bound paclitaxel plus oxaliplatin and S-1 (P-SOX), and SOX—in patients with advanced GC.
A retrospective analysis was conducted on 299 patients with advanced GC who received both neoadjuvant and adjuvant chemotherapy along with standard D2 radical gastrectomy. Among them, 81 patients received SOX plus sintilimab, 118 received the P-SOX regimen, and 100 received the SOX regimen. All patients were randomly assigned to training (70%) or validation (30%) cohorts using the R software sample function. Short-term efficacy, long-term survival outcomes, and adverse events were assessed across the three groups. Additionally, clinical factors associated with progression-free survival (PFS) were further investigated.
In terms of short-term efficacy, the SOX + sintilimab group had higher objective response rates [91.4% and 70.4% according to the tumor regression grade (TRG) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, respectively] than did the P-SOX (88.1% and 59.3%) and SOX groups (84.0% and 55.0%), although the intergroup differences were not statistically significant (P = 0.167). For long-term outcomes, the SOX + sintilimab group demonstrated significantly better OS rates at 1 year (98.8%), 18 months (92.6%), 2 years (84.0%), and 3 years (48.1%) than did the P-SOX (93.2%, 86.4%, 71.2%, 30.5%) and SOX (91.0%, 84.0%, 72.0%, 29.0%) groups, with the 3-year overall survival (OS) difference being statistically significant (P = 0.007). Similarly, PFS rates in the SOX + sintilimab group (1 year: 92.6%; 18 months: 77.8%; 2 years: 65.4%; 3 years: 35.8%) were significantly greater than those in the P-SOX (82.2%, 68.6%, 53.4%, 26.3%) and SOX (77.0%, 66.0%, 43.0%, 27.0%) groups, with significant differences at 1 year (P = 0.021) and 2 years (P = 0.011). In terms of safety, grade 1-2 gastrointestinal reactions, peripheral neuropathy, and alopecia were the main TRAEs across groups. The P-SOX group had a significantly greater incidence of alopecia (54.2% vs 53.0% vs 23.5%, P = 0.009) and more cases of grade 2 alopecia (6.8% vs 1.2%), potentially due to the accumulation of triple-agent toxicity. No significant intergroup differences were observed in hematologic toxicity or liver dysfunction (all P > 0.05).
Compared with the SOX and P-SOX regimens, the SOX plus sintilimab combination demonstrated significantly improved short- and long-term efficacy with favorable safety, with superior advantages in terms of 2- and 3-year OS and early PFS, suggesting that this combination is a more promising therapeutic option for patients with advanced GC. Patients who achieved good perioperative chemotherapy responses (meeting the TRG and RECIST 1.1 criteria) and had tumor diameters ≤ 2 cm, well-differentiated histology, earlier cTNM stages, and no lymph node metastasis had a better prognosis.
Core Tip: This study demonstrated that the SOX combined with sintilimab (PD-1 inhibitor) significantly improved long-term survival outcomes in patients with advanced gastric cancer (GC) compared with P-SOX (albumin-bound paclitaxel plus SOX) or SOX alone, with superior 3-year overall survival (48.1% vs 30.5% and 29.0%) and early progression-free survival rates. The regimen also maintains a favorable safety profile, suggesting that it is a promising perioperative treatment option. The key prognostic factors include a tumor diameter ≤ 2 cm, well-differentiated histology, and negative lymph node status. These findings support the integration of immunotherapy into neoadjuvant strategies for locally advanced GC.