Italian prospective observational RealFLOT study: Four-year update.

Abstract

370 Background: For patients (pts) with resectable gastric or gastroesophageal junction adenocarcinoma who are candidates for intensive therapy, the FLOT regimen (fluorouracil, oxaliplatin, docetaxel) represents the standard backbone chemotherapy (CT) in perioperative setting. The Italian RealFLOT multicenter observational study investigated the feasibility, safety, and efficacy of perioperative FLOT in a real-world setting. Methods: In this updated analysis of the RealFLOT trial, the long-term feasibility, safety, and efficacy of FLOT were investigated, including endpoints such as disease-free survival (DFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). Survival probabilities were estimated by the Kaplan–Meier method and compared using the log-rank test. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by Cox regression analysis. Results: A total of 307 pts were enrolled, most with stage III disease (65.1%), gastric primary (57.0%), and non-intestinal histology (46.5%). High microsatellite instability (MSI-H) was detected in 13 of 148 pts (8.8% ) and HER2 positivity in 20 of 147 (13.6% ) of tested cases. Among pts receiving perioperative FLOT, 171 (55.7%) completed at least four full-dose cycles. Surgery was performed in 283 cases (92.2%), with 222 (72.3%) subsequently proceeding to postoperative treatment. During the neoadjuvant phase, CT delays occurred in 216 pts (70.6%) and treatment discontinuation in 15 pts (4.9%). Gastrointestinal toxicity represented the most frequent adverse event (65.9% in the preoperative and 67.6% in the postoperative setting, with grade 3–4 events occurred in 24 pts (11.3%). In the postoperative phase, FLOT was administered to 71.1% of pts although delays were reported in 71 pts (32.7%) and treatment discontinuations in 31 pts(14.2%). Among those who underwent surgery, an R0 resection was achieved in 261 of 280 evaluable cases (93.2%). With a median follow-up of 31.2 months (95% CI, 25.5–37.8), median DFS was 25.5 months (95% CI, 17.8–33.1) and median OS was 73.5 months (95% CI, 36.5–not estimable). Pathological CR was achieved in 9.0% of patients, and MPR in 28.2%. Both DFS and OS were significantly improved in pts achieving pCR (HR 0.22; 95% CI, p=0.001 and HR 0.16; 95% CI, p=0.004, respectively) or MPR (HR 0.18; 95% CI, p<0.001 and HR 0.14; 95% CI, p<0.001, respectively). Conversely, pts with advanced postoperative stage achieved shorter mDFS (12.6 vs 73.4 months; HR 3.22; 95% CI, p<0.001) and mOS (23.9 vs 85.2 months; HR 2.94; 95% CI, p<0.001). Notably, OS was significantly prolonged in patients with MSI-H tumors (HR 0.00 [0.01–NE]; 95% CI, p=0.029). Conclusions: Updated real-world evidence confirms the feasibility and efficacy of perioperative FLOT in routine clinical practice. Prognostic outcomes are influenced by pCR, MPR, postoperative stage, and MSI-H status.