Neoadjuvant PD-1 inhibitor combined with FLOT versus SOX for locally advanced gastric cancer: a retrospective cohort...

Neoadjuvant immunochemotherapy is increasingly used for resectable locally advanced gastric cancer (LAGC) and gastroesophageal junction (EGJ) adenocarcinoma, yet the optimal chemotherapy backbone for PD-1 blockade remains unclear. We compared neoadjuvant PD-1 inhibitor plus S-1+oxaliplatin (SOX) versus PD-1 inhibitor plus 5-FU+oxaliplatin+Docetaxel+Leucovorin (FLOT) in a real-world cohort.

This single-center retrospective study included patients with resectable, HER2-negative LAGC/EGJ adenocarcinoma (cT3-4b, any N+, M0; ECOG 0-1) treated between July 2020 and July 2025. Patients received neoadjuvant PD-1 inhibitor plus SOX or PD-1 inhibitor plus FLOT (3-5 cycles) followed by D2 gastrectomy. The primary endpoint was pathological complete response (pCR). Secondary endpoints included major pathological response (MPR), radiologic response (RECIST v1.1), perioperative outcomes, treatment-related adverse events (CTCAE v5.0), recurrence-free survival (RFS), and overall survival (OS). Survival was analyzed using Kaplan-Meier methods and Cox proportional hazards models.

Overall, 247 patients were enrolled (PD-1+SOX, n=141; PD-1+FLOT, n=106) with comparable baseline characteristics. Radiologic outcomes were similar between groups (ORR: 70.92% vs 66.98%, p=0.507; DCR: 87.23% vs 85.85%, p=0.752). Pathological responses did not differ significantly (pCR: 20.57% vs 16.98%, p=0.477; MPR: 37.59% vs 31.13%, p=0.292). Any-grade treatment-related adverse events occurred in 67.38% and 75.47% of patients, and grade ≥3 events in 19.15% and 26.42%, respectively; no treatment-related deaths occurred. R0 resection rates were high (100% vs 99.06%). Operative time and estimated blood loss were higher in the PD-1+FLOT group (p=0.010 and p=0.040), while postoperative complication rates were comparable. With median follow-up of 21 months (12-52) and 20 months (10-46), there were no significant differences in OS (HR 1.155, 95% CI 0.624-2.138) or RFS (HR 0.805, 95% CI 0.461-1.405). In multivariable analyses, non-MPR was an independent risk factor for both OS and RFS.

Neoadjuvant PD-1 inhibitor plus SOX and plus FLOT yielded comparable response rates, survival outcomes, and safety profiles in patients with resectable LAGC/EGJ adenocarcinoma. PD-1+SOX was associated with less operative burden, and MPR remained independently associated with OS and RFS, supporting its value for risk stratification and treatment optimization.