Comparative efficacy of adjuvant FOLFOX vs. FLOT following neoadjuvant FLOT in patients with locally advanced gastric cancer.

Abstract

Background/aim: Perioperative FLOT is considered the gold standard treatment for locally advanced gastric cancer. However, in the adjuvant setting, chemotherapy intolerance has brought de-escalation strategies to the forefront as an important area of research. This study aimed to compare the efficacy of adjuvant FLOT and FOLFOX regimens in enhancing survival outcomes in patients with locally advanced gastric cancer who underwent surgical resection following neoadjuvant FLOT treatment.

Materials and methods: Patients with locally advanced gastric cancer (cT2-4, N0-3) who received four cycles of neoadjuvant FLOT and subsequently underwent surgery at Ankara Bilkent City Hospital between January 2018 and September 2024 were retrospectively evaluated. Disease-free survival (DFS) and overall survival (OS) outcomes were compared to patients receiving adjuvant FOLFOX or FLOT. Clinical variables such as disease stage and response to neoadjuvant therapy were also analyzed to determine their impact on DFS and OS.

Results: The analysis included 171 patients, with a median age of 59 years and a median follow-up duration of 16.1 months. At 16 months, the DFS and OS rates were 66% and 82%, respectively. Of the 171 patients, 105 received adjuvant FLOT, 37 received FOLFOX, and 29 received no adjuvant therapy. Statistical analysis revealed no significant differences 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. However, the advanced disease stage and lack of pathological response to neoadjuvant FLOT were associated with decreased DFS and OS, highlighting these factors as potential prognostic indicators.

Conclusion: Among patients undergoing surgery after neoadjuvant FLOT, adjuvant FOLFOX showed comparable efficacy to FLOT, suggesting its potential as an alternative option, particularly for patients with deteriorated ECOG PS or those who developed chemotherapy intolerance postoperatively. These findings inform treatment strategies and optimize adjuvant therapy selection based on individual patient profiles.