Comparative efficacy of adjuvant FOLFOX versus FLOT following neoadjuvant FLOT in locally advanced gastric cancer.

Abstract

e16120 Background: Perioperative FLOT is the gold-standard treatment for locally advanced gastric cancer (LAGC). However, the tolerability of adjuvant chemotherapy poses challenges, with many patients unable to complete treatment due to toxicity. This study compared the efficacy of adjuvant FLOT and FOLFOX in improving survival outcomes in LAGC patients who underwent surgery after neoadjuvant FLOT. Methods: This retrospective, single-center study included patients with histologically confirmed LAGC (cT2-4, N0-3) treated at Ankara Bilkent City Hospital (January 2018 – September 2024). All patients received four cycles of neoadjuvant FLOT followed by surgical resection. Postoperatively, patients were stratified into three groups: adjuvant FLOT, FOLFOX, or no adjuvant therapy. Kaplan-Meier survival analysis assessed disease-free survival (DFS) and overall survival (OS). Cox regression identified independent prognostic factors, including tumor regression grade (TRG), stage, and ECOG performance status (PS). Results: Among 171 patients (median age: 59 years; 77% male; median follow-up: 16.1 months), 105 received adjuvant FLOT, 37 received FOLFOX, and 29 received no adjuvant therapy. At 16 months, DFS and OS rates were 66% and 82%, respectively. No significant differences were observed in DFS (HR: 0.63, 95% CI: 0.30-1.33, p = 0.229) or OS (HR: 0.76, 95% CI: 0.24-2.37, p = 0.635) between the FLOT and FOLFOX groups. Advanced stage and absence of pathological response (TRG3) were associated with worse DFS (HR: 5.56, 95% CI: 2.38-14.29, p < 0.001) and OS (HR: 7.69, 95% CI: 2.33-25.00, p < 0.001). Patients without adjuvant chemotherapy exhibited significantly inferior survival compared to FLOT or FOLFOX groups (DFS HR: 10.00, p < 0.001; OS HR: 9.09, p < 0.001). Conclusions: Adjuvant FOLFOX demonstrated comparable efficacy to FLOT, offering a feasible alternative for patients with LAGC who exhibit poor ECOG PS or intolerance to intensive chemotherapy. These results highlight the importance of individualized treatment strategies in optimizing outcomes and minimizing toxicities in gastric cancer management. Further prospective studies are warranted to validate these findings and explore biomarkers that could refine patient selection for adjuvant regimens.