Real world outcomes of perioperative FLOT in an Italian cohort of resectable gastric cancer: long term follow-up of prospective observational Real-FLOT study

For patients with resectable gastric or gastroesophageal junction adenocarcinoma candidates for intensive therapy, the FLOT (fluorouracil, oxaliplatin, docetaxel) represents the standard perioperative chemotherapy. The Italian RealFLOT multicentre observational study investigated the feasibility, safety, and efficacy of perioperative FLOT in a real-world setting. In this updated analysis of the RealFLOT trial, long-term feasibility, safety, and efficacy of FLOT were investigated. Endpoints included disease-free survival (DFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). Survival probabilities were estimated by Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated by Cox regression analysis. A total of 307 patients were enrolled, most with stage III disease (65.1%), gastric primary (57.0%), and non-intestinal histology (46.6%). Microsatellite instability (MSI) was detected in 8.8% and HER2 positivity in 13.6% of tested cases. Among patients receiving preoperative FLOT, 177 (57.6%) completed at least four full-dose cycles. Surgery was performed in 283 cases (92.2%), with 221 (72.0%) proceeding to postoperative treatment. Chemotherapy delays and discontinuations occurred in 90 (29.3%) and 15 patients (4.9%) preoperatively, and in 65 (21.2%) and 25 patients (8.1%) postoperatively. Gastrointestinal toxicity represented the most frequent adverse event (64.8% preoperative, 65.2% postoperative), with grade 3–4 events in 17 (5.5%) and 24 patients (10.9%), respectively. R0 resection was achieved in 261 of 280 evaluable cases (92.9%). 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). pCR was achieved in 8.6%, and MPR in 26.7%. Both DFS and OS were significantly improved with pCR (HR 0.22; 95% CI, p = 0.001; HR 0.16; 95% CI, p = 0.004) or MPR (HR 0.18; 95% CI, p < 0.001; HR 0.14; 95% CI, p < 0.001). Notably, OS was significantly prolonged in patients with MSI tumors (HR 0.00; 95% CI, p = 0.029). 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 status.