Nab-paclitaxel-oxaliplatin-S-1 vs FOLFOX in locally advanced gastric cancer: Efficacy and postoperative disease-free survival prediction

Abstract

BACKGROUND

Locally advanced gastric cancer remains associated with a considerable risk of recurrence despite perioperative chemotherapy and radical surgery. Folinic acid, fluorouracil, and oxaliplatin is widely used, whereas nab-paclitaxel, oxaliplatin, and S-1 has shown potential antitumor activity in clinical practice. However, real-world comparative evidence between these regimens and postoperative tools for individualized disease-free survival (DFS) prediction remain limited. We hypothesized that clinicopathological and treatment-response variables could support postoperative recurrence risk stratification.

AIM

To compare the short-term response, long-term outcomes, and safety of the FOLFOX and P-SOX regimens in patients with gastric cancer. Using clinicopathological data, treatment response, and follow-up information, we applied least absolute shrinkage and selection operator Cox regression to select key factors associated with DFS and constructed a nomogram for predicting DFS at 18 months, 24 months, and 36 months.

METHODS

This retrospective study included 181 patients with advanced gastric cancer who received preoperative and postoperative chemotherapy followed by standard D2 radical gastrectomy. Clinical data were collected from two centers: Qinghai University Affiliated Hospital and Qinghai Red Cross Hospital. Among these patients, 113 received the P-SOX regimen, and 68 received the FOLFOX regimen. In this real-world retrospective study, the choice between P-SOX and FOLFOX was based on physicians’ comprehensive assessment of patient condition, tumor status, treatment tolerance, economic factors, and patient preference rather than on random allocation. Patients were screened according to predefined inclusion and exclusion criteria, and the detailed eligibility criteria and treatment protocols are presented in the Supplementary material. Using the sample function in R, the cohort was randomly divided into a training set and a validation set at a 7:3 ratio for model development and internal validation, respectively. Short-term treatment response, long-term outcomes, and adverse events were compared between the two treatment groups. Clinical factors associated with DFS were further analyzed.

RESULTS

According to response evaluation criteria in solid tumors 1.1, the objective response rate was 61.1% in the P-SOX group and 51.5% in the FOLFOX group, with no statistically significant difference between the two groups (P = 0.206). Analysis based on tumor regression grade (TRG) revealed that the pathological response rate was 31.0% in the P-SOX group and 23.5% in the FOLFOX group, and the difference was not statistically significant (P = 0.281). For long-term outcomes, Kaplan-Meier survival analysis revealed that the DFS and overall survival (OS) curves of the P-SOX group were slightly greater than those of the FOLFOX group, but the differences were not statistically significant. The log-rank P value was 0.420 for DFS and 0.704 for OS. Adverse events were generally manageable in both groups and were mainly mild to moderate. No significant differences were detected between the FOLFOX and P-SOX groups in terms of nausea and vomiting, liver function impairment, alopecia, peripheral sensory neuropathy, neutropenia, thrombocytopenia, or anemia (all P > 0.05). The distribution of leukopenia differed significantly between the two groups (P = 0.027), with a higher proportion of grade 1 leukopenia in the P-SOX group, whereas grade 2 and grade 4 leukopenia were slightly more frequent in the FOLFOX group. Overall, the two regimens were comparable in terms of safety profiles, without an apparent increase in severe toxicity.

CONCLUSION

In summary, compared with the FOLFOX regimen, the P-SOX regimen tended to be favorable for short-term response and long-term survival outcomes, with numerically better OS and DFS. These findings suggest that P-SOX may represent a promising perioperative treatment option for patients with advanced gastric cancer. In addition, patients with a good perioperative treatment response, reflected by an improved TRG, a smaller tumor diameter (≤ 2 cm), an earlier clinical tumor node metastasis stage, and well-differentiated tumors, generally had better survival outcomes.

Keywords: Gastric cancer; FOLFOX; P-SOX; Disease-free survival; Nomogram

Core Tip: This retrospective two-center study compared FOLFOX and P-SOX regimens in patients with locally advanced gastric cancer undergoing perioperative chemotherapy and D2 radical gastrectomy. P-SOX showed numerically higher radiological and pathological response rates than FOLFOX, but the differences were not statistically significant. Survival curves also suggested a favorable trend for P-SOX without significant disease-free survival or overall survival improvement. A least absolute shrinkage and selection operator-Cox-based nomogram incorporating clinical tumor node metastasis stage, tumor regression grade response, and pre-chemotherapy tumor diameter was developed to predict 18-month, 24-month, and 36-month disease-free survival, providing a practical tool for postoperative recurrence risk stratification.